IndraLab
Statements
sparser
"Overall, our two UAF1-USP12 structures not only reveal a series of structural changes of the enzyme that are connected to the binding site of UAF1 but also highlight the dynamic nature of three key loops, namely, BL2, BL3, and the CC Loop, surrounding the catalytic site of the activated enzyme."
sparser
"Highlights d Free USP12 deubiquitinase is inactive and has several flexible structural elements d UAF1 and WDR20 can both activate USP12 without increasing its substrate affinity d UAF1 and WDR20 bind USP12 at two distinct sites away from its catalytic center d Two distinct allosteric mechanisms underlie USP12 activation by UAF1 and WDR20
Ubiquitin-specific proteases (USPs) constitute the largest family of deubiquitinating enzymes, whose catalytic competency is often modulated by their binding partners through unknown mechanisms."
sparser
"Structural Comparisons of Activator-Bound USP12 and Ub-Conjugated USP46(A) Superposition of UAF1-bound USP12 and UAF1-WDR20-bound USP12 highlighting stabilization of BL1 and BL3 in the ternary complex.(B and C) A comparison between the UAF1-WDR20-bound USP12 and the Ub-conjugated USP46 structures, focusing on the stabilized PK Loop, the regularized PK Helix, and the F219 residue at the Fingers-Palm domain junction. (D) A close-up view of BL1 and the catalytic cleft of USP12 in complex with UAF1 and WDR20."
reach
"While the Pinky Finger of USP12 in the UAF1-USP12-WDR20 complex adopts the same b strand conformation as seen in the UAF1-USP12 complex, F219 on the PK Helix becomes embedded in the pocket formed between the Fingers and the Palm domains, instead of being tucked underneath the Fingers domain ( Figures 3D, 5B , and 5C)."
sparser
"Recent structural work revealed how the WD-repeat protein UAF1 interacted with the catalytic domain of USP46 and USP12, which is facilitated predominantly through the “fingers” subdomain of the USP core, mediating long-range allosteric interactions eventually leading to enhanced enzyme efficiency ( xref , xref )."
reach
"Although the active site of USP12 in the UAF1-USP12 complex crystallized in F222 space group adopts the same topology as found in the free enzyme ( Figure S3F ), in the C2 space group structure, the USP12 Thumb domain features a series of major structural rearrangements at the catalytic cleft."
reach
"Although the active site of USP12 in the UAF1 and USP12 complex crystallized in F222 space group adopts the same topology as found in the free enzyme (XREF_SUPPLEMENTARY), in the C2 space group structure, the USP12 Thumb domain features a series of major structural rearrangements at the catalytic cleft."
reach
"While the Pinky Finger of USP12 in the UAF1-USP12-WDR20 complex adopts the same b strand conformation as seen in the UAF1-USP12 complex, F219 on the PK Helix becomes embedded in the pocket formed between the Fingers and the Palm domains, instead of being tucked underneath the Fingers domain ( Figures 3D, 5B , and 5C)."
reach
"While the Pinky Finger of USP12 in the UAF1, USP12, and WDR20 complex adopts the same beta-strand conformation as seen in the UAF1 and USP12 complex, F219 on the PK Helix becomes embedded in its pocket formed between the Fingers and Palm domains, instead of being tucked underneath the Fingers domain (XREF_FIG, XREF_FIG, XREF_FIG)."
sparser
"Overall, our two UAF1-USP12 structures not only reveal a series of structural changes of the enzyme that are connected to the binding site of UAF1 but also highlight the dynamic nature of three key loops, namely, BL2, BL3, and the CC Loop, surrounding the catalytic site of the activated enzyme."
sparser
"Highlights d Free USP12 deubiquitinase is inactive and has several flexible structural elements d UAF1 and WDR20 can both activate USP12 without increasing its substrate affinity d UAF1 and WDR20 bind USP12 at two distinct sites away from its catalytic center d Two distinct allosteric mechanisms underlie USP12 activation by UAF1 and WDR20
Ubiquitin-specific proteases (USPs) constitute the largest family of deubiquitinating enzymes, whose catalytic competency is often modulated by their binding partners through unknown mechanisms."
sparser
"Structural Comparisons of Activator-Bound USP12 and Ub-Conjugated USP46(A) Superposition of UAF1-bound USP12 and UAF1-WDR20-bound USP12 highlighting stabilization of BL1 and BL3 in the ternary complex.(B and C) A comparison between the UAF1-WDR20-bound USP12 and the Ub-conjugated USP46 structures, focusing on the stabilized PK Loop, the regularized PK Helix, and the F219 residue at the Fingers-Palm domain junction. (D) A close-up view of BL1 and the catalytic cleft of USP12 in complex with UAF1 and WDR20."
reach
"While the Pinky Finger of USP12 in the UAF1-USP12-WDR20 complex adopts the same b strand conformation as seen in the UAF1-USP12 complex, F219 on the PK Helix becomes embedded in the pocket formed between the Fingers and the Palm domains, instead of being tucked underneath the Fingers domain ( Figures 3D, 5B , and 5C)."
sparser
"Recent structural work revealed how the WD-repeat protein UAF1 interacted with the catalytic domain of USP46 and USP12, which is facilitated predominantly through the “fingers” subdomain of the USP core, mediating long-range allosteric interactions eventually leading to enhanced enzyme efficiency ( xref , xref )."
reach
"Although the active site of USP12 in the UAF1-USP12 complex crystallized in F222 space group adopts the same topology as found in the free enzyme ( Figure S3F ), in the C2 space group structure, the USP12 Thumb domain features a series of major structural rearrangements at the catalytic cleft."
reach
"Although the active site of USP12 in the UAF1 and USP12 complex crystallized in F222 space group adopts the same topology as found in the free enzyme (XREF_SUPPLEMENTARY), in the C2 space group structure, the USP12 Thumb domain features a series of major structural rearrangements at the catalytic cleft."
reach
"While the Pinky Finger of USP12 in the UAF1-USP12-WDR20 complex adopts the same b strand conformation as seen in the UAF1-USP12 complex, F219 on the PK Helix becomes embedded in the pocket formed between the Fingers and the Palm domains, instead of being tucked underneath the Fingers domain ( Figures 3D, 5B , and 5C)."
reach
"While the Pinky Finger of USP12 in the UAF1, USP12, and WDR20 complex adopts the same beta-strand conformation as seen in the UAF1 and USP12 complex, F219 on the PK Helix becomes embedded in its pocket formed between the Fingers and Palm domains, instead of being tucked underneath the Fingers domain (XREF_FIG, XREF_FIG, XREF_FIG)."
sparser
"The k cat and K M values are presented as means ± SD (n = 3), and the K D values were obtained through steady-state analysis (see Supplemental Experimental Procedures for technical discussion). (B) Time course of USP12 modification by the suicidal Ub-VME substrate in the absence or presence of UAF1 and WDR20. (C) Time course of LRGG-AMC (top) in contrast to Ub-AMC (bottom) hydrolysis by USP12 (green), UAF1-USP12 (orange), and USP12-WDR20 (red)."
sparser
"Highlights d Free USP12 deubiquitinase is inactive and has several flexible structural elements d UAF1 and WDR20 can both activate USP12 without increasing its substrate affinity d UAF1 and WDR20 bind USP12 at two distinct sites away from its catalytic center d Two distinct allosteric mechanisms underlie USP12 activation by UAF1 and WDR20
Ubiquitin-specific proteases (USPs) constitute the largest family of deubiquitinating enzymes, whose catalytic competency is often modulated by their binding partners through unknown mechanisms."
sparser
"Structural Comparisons of Activator-Bound USP12 and Ub-Conjugated USP46(A) Superposition of UAF1-bound USP12 and UAF1-WDR20-bound USP12 highlighting stabilization of BL1 and BL3 in the ternary complex.(B and C) A comparison between the UAF1-WDR20-bound USP12 and the Ub-conjugated USP46 structures, focusing on the stabilized PK Loop, the regularized PK Helix, and the F219 residue at the Fingers-Palm domain junction. (D) A close-up view of BL1 and the catalytic cleft of USP12 in complex with UAF1 and WDR20."
reach
"While the Pinky Finger of USP12 in the UAF1-USP12-WDR20 complex adopts the same b strand conformation as seen in the UAF1-USP12 complex, F219 on the PK Helix becomes embedded in the pocket formed between the Fingers and the Palm domains, instead of being tucked underneath the Fingers domain ( Figures 3D, 5B , and 5C)."
sparser
"The k cat and K M values are presented as means ± SD (n = 3), and the K D values were obtained through steady-state analysis (see Supplemental Experimental Procedures for technical discussion). (B) Time course of USP12 modification by the suicidal Ub-VME substrate in the absence or presence of UAF1 and WDR20. (C) Time course of LRGG-AMC (top) in contrast to Ub-AMC (bottom) hydrolysis by USP12 (green), UAF1-USP12 (orange), and USP12-WDR20 (red)."
sparser
"Highlights d Free USP12 deubiquitinase is inactive and has several flexible structural elements d UAF1 and WDR20 can both activate USP12 without increasing its substrate affinity d UAF1 and WDR20 bind USP12 at two distinct sites away from its catalytic center d Two distinct allosteric mechanisms underlie USP12 activation by UAF1 and WDR20
Ubiquitin-specific proteases (USPs) constitute the largest family of deubiquitinating enzymes, whose catalytic competency is often modulated by their binding partners through unknown mechanisms."
sparser
"Structural Comparisons of Activator-Bound USP12 and Ub-Conjugated USP46(A) Superposition of UAF1-bound USP12 and UAF1-WDR20-bound USP12 highlighting stabilization of BL1 and BL3 in the ternary complex.(B and C) A comparison between the UAF1-WDR20-bound USP12 and the Ub-conjugated USP46 structures, focusing on the stabilized PK Loop, the regularized PK Helix, and the F219 residue at the Fingers-Palm domain junction. (D) A close-up view of BL1 and the catalytic cleft of USP12 in complex with UAF1 and WDR20."
reach
"While the Pinky Finger of USP12 in the UAF1-USP12-WDR20 complex adopts the same b strand conformation as seen in the UAF1-USP12 complex, F219 on the PK Helix becomes embedded in the pocket formed between the Fingers and the Palm domains, instead of being tucked underneath the Fingers domain ( Figures 3D, 5B , and 5C)."
sparser
"Recent structural work revealed how the WD-repeat protein UAF1 interacted with the catalytic domain of USP46 and USP12, which is facilitated predominantly through the “fingers” subdomain of the USP core, mediating long-range allosteric interactions eventually leading to enhanced enzyme efficiency ( xref , xref )."
sparser
"Although the exact function of p80/Uaf1 in viral DNA replication remains unclear, this WD40 repeats-containing protein is known to interact with the de-ubiquitinating enzymes Usp1, Usp12 and Usp46, whose substrates include PCNA, histones H2A and H2B and Fanconi anaemia complementation group D type 2, a component of the Fanconi anaemia pathway [ xref , xref ]."
sparser
"Recent structural work revealed how the WD-repeat protein UAF1 interacted with the catalytic domain of USP46 and USP12, which is facilitated predominantly through the “fingers” subdomain of the USP core, mediating long-range allosteric interactions eventually leading to enhanced enzyme efficiency ( xref , xref )."
sparser
"Although the exact function of p80/Uaf1 in viral DNA replication remains unclear, this WD40 repeats-containing protein is known to interact with the de-ubiquitinating enzymes Usp1, Usp12 and Usp46, whose substrates include PCNA, histones H2A and H2B and Fanconi anaemia complementation group D type 2, a component of the Fanconi anaemia pathway [ xref , xref ]."
reach
"Our previous observations for the LNCaP cell line that express AR FL but not AR Vs have demonstrated that USP12 silencing causes a decrease in transcript expression of all the AR target genes [XREF_BIBR] supporting our data that AR Vs are not targeted by USP12 in the AR V expressing CWR22Rv1 cell line."
reach
"This further confirms that each complex member alone has a limited effect on AR activity but in combination the Usp12 complex significantly increases AR transcriptional activity implying that targeting any of the binding partners should offer the same efficacy as targeting Usp12 alone."
reach
"Our previous observations for the LNCaP cell line that express AR FL but not AR Vs have demonstrated that USP12 silencing causes a decrease in transcript expression of all the AR target genes [XREF_BIBR] supporting our data that AR Vs are not targeted by USP12 in the AR V expressing CWR22Rv1 cell line."
sparser
"Highlights d Free USP12 deubiquitinase is inactive and has several flexible structural elements d UAF1 and WDR20 can both activate USP12 without increasing its substrate affinity d UAF1 and WDR20 bind USP12 at two distinct sites away from its catalytic center d Two distinct allosteric mechanisms underlie USP12 activation by UAF1 and WDR20
Ubiquitin-specific proteases (USPs) constitute the largest family of deubiquitinating enzymes, whose catalytic competency is often modulated by their binding partners through unknown mechanisms."
sparser
"Structural Comparisons of Activator-Bound USP12 and Ub-Conjugated USP46(A) Superposition of UAF1-bound USP12 and UAF1-WDR20-bound USP12 highlighting stabilization of BL1 and BL3 in the ternary complex.(B and C) A comparison between the UAF1-WDR20-bound USP12 and the Ub-conjugated USP46 structures, focusing on the stabilized PK Loop, the regularized PK Helix, and the F219 residue at the Fingers-Palm domain junction. (D) A close-up view of BL1 and the catalytic cleft of USP12 in complex with UAF1 and WDR20."
reach
"While the Pinky Finger of USP12 in the UAF1-USP12-WDR20 complex adopts the same b strand conformation as seen in the UAF1-USP12 complex, F219 on the PK Helix becomes embedded in the pocket formed between the Fingers and the Palm domains, instead of being tucked underneath the Fingers domain ( Figures 3D, 5B , and 5C)."
reach
"Importantly, overexpression of Usp12 deubiquitinated both PHLPP and PHLPPL and this elevated the steady-state levels of the enzymes, while overexpression of an enzymatically inactive Usp12 C48A mutant failed to elevate PHLPP and PHLPPL levels suggesting the importance of Usp12 enzymatic activity for phosphatase regulation."
sparser
"Highlights d Free USP12 deubiquitinase is inactive and has several flexible structural elements d UAF1 and WDR20 can both activate USP12 without increasing its substrate affinity d UAF1 and WDR20 bind USP12 at two distinct sites away from its catalytic center d Two distinct allosteric mechanisms underlie USP12 activation by UAF1 and WDR20
Ubiquitin-specific proteases (USPs) constitute the largest family of deubiquitinating enzymes, whose catalytic competency is often modulated by their binding partners through unknown mechanisms."
sparser
"Structural Comparisons of Activator-Bound USP12 and Ub-Conjugated USP46(A) Superposition of UAF1-bound USP12 and UAF1-WDR20-bound USP12 highlighting stabilization of BL1 and BL3 in the ternary complex.(B and C) A comparison between the UAF1-WDR20-bound USP12 and the Ub-conjugated USP46 structures, focusing on the stabilized PK Loop, the regularized PK Helix, and the F219 residue at the Fingers-Palm domain junction. (D) A close-up view of BL1 and the catalytic cleft of USP12 in complex with UAF1 and WDR20."
reach
"While the Pinky Finger of USP12 in the UAF1-USP12-WDR20 complex adopts the same b strand conformation as seen in the UAF1-USP12 complex, F219 on the PK Helix becomes embedded in the pocket formed between the Fingers and the Palm domains, instead of being tucked underneath the Fingers domain ( Figures 3D, 5B , and 5C)."
reach
"Importantly, overexpression of Usp12 deubiquitinated both PHLPP and PHLPPL and this elevated the steady-state levels of the enzymes, while overexpression of an enzymatically inactive Usp12 C48A mutant failed to elevate PHLPP and PHLPPL levels suggesting the importance of Usp12 enzymatic activity for phosphatase regulation."
sparser
"Recent structural work revealed how the WD-repeat protein UAF1 interacted with the catalytic domain of USP46 and USP12, which is facilitated predominantly through the “fingers” subdomain of the USP core, mediating long-range allosteric interactions eventually leading to enhanced enzyme efficiency ( xref , xref )."
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4
9
UAF1 affects USP12
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10
eidos
"Highlights d Free USP12 deubiquitinase is inactive and has several flexible structural elements d UAF1 and WDR20 can both activate USP12 without increasing its substrate affinity d UAF1 and WDR20 bind USP12 at two distinct sites away from its catalytic center d Two distinct allosteric mechanisms underlie USP12 activation by UAF1 and WDR20 Ubiquitin-specific proteases ( USPs ) constitute the largest family of deubiquitinating enzymes , whose catalytic competency is often modulated by their binding partners through unknown mechanisms ."
sparser
"Recent structural work revealed how the WD-repeat protein UAF1 interacted with the catalytic domain of USP46 and USP12, which is facilitated predominantly through the “fingers” subdomain of the USP core, mediating long-range allosteric interactions eventually leading to enhanced enzyme efficiency ( xref , xref )."
USP12 affects cell population proliferation
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6
USP12 inhibits cell population proliferation.
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5
USP12 activates cell population proliferation.
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1
USP12 activates cell population proliferation. 1 / 1
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1
sparser
"Although the exact function of p80/Uaf1 in viral DNA replication remains unclear, this WD40 repeats-containing protein is known to interact with the de-ubiquitinating enzymes Usp1, Usp12 and Usp46, whose substrates include PCNA, histones H2A and H2B and Fanconi anaemia complementation group D type 2, a component of the Fanconi anaemia pathway [ xref , xref ]."
USP12 affects apoptotic process
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1
6
USP12 activates apoptotic process.
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1
5
USP12 activates apoptotic process. 6 / 6
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1
5
eidos
"In vivo experiments showed that USP12-knockdown could suppress tumor growth in mice , and immuno-blotting revealed that USP12 could induce G2 / M arrest through the cyclin dependent kinase 1 / cyclinB1 axis , and trigger apoptosis via the p38 / mitogen-activated protein kinase pathway ."
reach
"Invivo experiments showed that USP12-knockdown could suppress tumor growth in mice, and immuno blotting revealed that USP12 could induce G2/M arrest through the cyclin dependent kinase1 and cyclinB1 axis, and trigger apoptosis via the p38 and mitogen activated protein kinase pathway."
USP12 inhibits apoptotic process.
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1
USP12 inhibits apoptotic process. 1 / 1
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1
sparser
"Although the exact function of p80/Uaf1 in viral DNA replication remains unclear, this WD40 repeats-containing protein is known to interact with the de-ubiquitinating enzymes Usp1, Usp12 and Usp46, whose substrates include PCNA, histones H2A and H2B and Fanconi anaemia complementation group D type 2, a component of the Fanconi anaemia pathway [ xref , xref ]."
reach
"The dauer larva-constitutive C. elegans phenotype caused by defective DAF-7 and TGF-beta signaling was enhanced and suppressed, respectively, by ubh-1 deletion and overexpression in the loss-of-function genetic backgrounds of daf7, daf-1 and TGF-betaRI, and daf4 and R-SMAD, but not of daf-8 and R-SMAD."
reach
"The dauer larva-constitutive C. elegans phenotype caused by defective DAF-7 and TGF-beta signaling was enhanced and suppressed, respectively, by ubh-1 deletion and overexpression in the loss-of-function genetic backgrounds of daf7, daf-1 and TGF-betaRI, and daf4 and R-SMAD, but not of daf-8 and R-SMAD."
reach
"Here, we show that the deubiquitinating enzyme UBH-1 in Caenorhabditis elegans and its human homolog, ubiquitin C-terminal hydrolase-L1 (UCH-L1), stimulate DAF-7 and TGF-beta signaling, suggesting that this mode of regulation of TGF-beta signaling is conserved across animal species."
reach
"Here, we show that the deubiquitinating enzyme UBH-1 in Caenorhabditis elegans and its human homolog, ubiquitin C-terminal hydrolase-L1 (UCH-L1), stimulate DAF-7 and TGF-beta signaling, suggesting that this mode of regulation of TGF-beta signaling is conserved across animal species."
sparser
"Although the exact function of p80/Uaf1 in viral DNA replication remains unclear, this WD40 repeats-containing protein is known to interact with the de-ubiquitinating enzymes Usp1, Usp12 and Usp46, whose substrates include PCNA, histones H2A and H2B and Fanconi anaemia complementation group D type 2, a component of the Fanconi anaemia pathway [ xref , xref ]."
reach
"Here, we show that the deubiquitinating enzyme UBH-1 in Caenorhabditis elegans and its human homolog, ubiquitin C-terminal hydrolase-L1 (UCH-L1), stimulate DAF-7 and TGF-beta signaling, suggesting that this mode of regulation of TGF-beta signaling is conserved across animal species."
reach
"Here, we show that the deubiquitinating enzyme UBH-1 in Caenorhabditis elegans and its human homolog, ubiquitin C-terminal hydrolase-L1 (UCH-L1), stimulate DAF-7 and TGF-beta signaling, suggesting that this mode of regulation of TGF-beta signaling is conserved across animal species."
USP12 affects Histone_H2B
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5
reach
"This study demonstrated that AKT-mTOR hyperactivation resulted in USP12 downregulation, which in turn increased the production of protumourigenic chemokine in NSCLC, indicating that USP12 is a regulatory node in oncogenic mutation-driven TME development.The tumour suppressive function conveyed by USP12 is virtually related to the control of protumourigenic chemokine expression."
reach
"Collectively, these data indicate that dysregulated chemokine expression caused by USP12 downregulation, as exemplified by CXCL1 and CCL2, is important for the development of immune-suppressive TME.To validate whether the role of USP12 on TME reprogramming has pathological relevance in human NSCLC, we investigated the relationship between TAMs and USP12 expression in human NSCLC cohorts."
reach
"Given that USP12 negatively regulated protumourigenic chemokine expression and exerted a tumour-suppressive effect in immune-competent mice but not in immune-deficient mice, it seems intuitive to speculate that USP12 downregulation in tumours may help establish a favourable microenvironment for tumour growth."
Valproic acid affects USP12
3
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Valproic acid decreases the amount of USP12.
2
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Valproic acid methylates USP12.
1
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WDR48 affects F222
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3
reach
"Although the active site of USP12 in the UAF1-USP12 complex crystallized in F222 space group adopts the same topology as found in the free enzyme ( Figure S3F ), in the C2 space group structure, the USP12 Thumb domain features a series of major structural rearrangements at the catalytic cleft."
reach
"Although the active site of USP12 in the UAF1 and USP12 complex crystallized in F222 space group adopts the same topology as found in the free enzyme (XREF_SUPPLEMENTARY), in the C2 space group structure, the USP12 Thumb domain features a series of major structural rearrangements at the catalytic cleft."
WDR48 affects F219
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3
reach
"While the Pinky Finger of USP12 in the UAF1-USP12-WDR20 complex adopts the same b strand conformation as seen in the UAF1-USP12 complex, F219 on the PK Helix becomes embedded in the pocket formed between the Fingers and the Palm domains, instead of being tucked underneath the Fingers domain ( Figures 3D, 5B , and 5C)."
reach
"While the Pinky Finger of USP12 in the UAF1, USP12, and WDR20 complex adopts the same beta-strand conformation as seen in the UAF1 and USP12 complex, F219 on the PK Helix becomes embedded in its pocket formed between the Fingers and Palm domains, instead of being tucked underneath the Fingers domain (XREF_FIG, XREF_FIG, XREF_FIG)."
WDR proteins affects USP12
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3
reach
"Together, these structural studies suggest that binding of the WDR proteins to USP12 or USP46 relatively far from the active site results in the rearrangement of several structural elements, which propagates to the catalytic triad increasing enzyme catalysis.These recent structural and biochemical studies complement in vivo studies of the USP-46/WDR-48/WDR-20 complex in C. elegans."
USP12 affects cell cycle
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2
1
USP12 activates cell cycle.
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1
1
USP12 inhibits cell cycle.
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1
USP12 inhibits cell cycle. 1 / 1
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1
USP12 affects WDR proteins
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3
reach
"Together, these structural studies suggest that binding of the WDR proteins to USP12 or USP46 relatively far from the active site results in the rearrangement of several structural elements, which propagates to the catalytic triad increasing enzyme catalysis.These recent structural and biochemical studies complement in vivo studies of the USP-46/WDR-48/WDR-20 complex in C. elegans."
USP12 affects PC
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3
USP12 affects F222
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3
reach
"Although the active site of USP12 in the UAF1-USP12 complex crystallized in F222 space group adopts the same topology as found in the free enzyme ( Figure S3F ), in the C2 space group structure, the USP12 Thumb domain features a series of major structural rearrangements at the catalytic cleft."
reach
"Although the active site of USP12 in the UAF1 and USP12 complex crystallized in F222 space group adopts the same topology as found in the free enzyme (XREF_SUPPLEMENTARY), in the C2 space group structure, the USP12 Thumb domain features a series of major structural rearrangements at the catalytic cleft."
USP12 affects F219
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3
reach
"While the Pinky Finger of USP12 in the UAF1-USP12-WDR20 complex adopts the same b strand conformation as seen in the UAF1-USP12 complex, F219 on the PK Helix becomes embedded in the pocket formed between the Fingers and the Palm domains, instead of being tucked underneath the Fingers domain ( Figures 3D, 5B , and 5C)."
reach
"While the Pinky Finger of USP12 in the UAF1, USP12, and WDR20 complex adopts the same beta-strand conformation as seen in the UAF1 and USP12 complex, F219 on the PK Helix becomes embedded in its pocket formed between the Fingers and Palm domains, instead of being tucked underneath the Fingers domain (XREF_FIG, XREF_FIG, XREF_FIG)."
USP12 affects Carcinoma, Non-Small-Cell Lung
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1
2
USP12 activates Carcinoma, Non-Small-Cell Lung.
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1
1
USP12 inhibits Carcinoma, Non-Small-Cell Lung.
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1
USP12 inhibits Carcinoma, Non-Small-Cell Lung. 1 / 1
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1
USP12 is modified
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1
1
1
F222 affects WDR48
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3
reach
"Although the active site of USP12 in the UAF1-USP12 complex crystallized in F222 space group adopts the same topology as found in the free enzyme ( Figure S3F ), in the C2 space group structure, the USP12 Thumb domain features a series of major structural rearrangements at the catalytic cleft."
reach
"Although the active site of USP12 in the UAF1 and USP12 complex crystallized in F222 space group adopts the same topology as found in the free enzyme (XREF_SUPPLEMENTARY), in the C2 space group structure, the USP12 Thumb domain features a series of major structural rearrangements at the catalytic cleft."
F219 affects WDR48
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3
reach
"While the Pinky Finger of USP12 in the UAF1-USP12-WDR20 complex adopts the same b strand conformation as seen in the UAF1-USP12 complex, F219 on the PK Helix becomes embedded in the pocket formed between the Fingers and the Palm domains, instead of being tucked underneath the Fingers domain ( Figures 3D, 5B , and 5C)."
reach
"While the Pinky Finger of USP12 in the UAF1, USP12, and WDR20 complex adopts the same beta-strand conformation as seen in the UAF1 and USP12 complex, F219 on the PK Helix becomes embedded in its pocket formed between the Fingers and Palm domains, instead of being tucked underneath the Fingers domain (XREF_FIG, XREF_FIG, XREF_FIG)."
Pirinixic acid affects USP12
2
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Bisphenol A affects USP12
2
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Bisphenol A methylates USP12.
1
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Bisphenol A decreases the amount of USP12.
1
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Vehicle Emissions affects USP12
2
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Usp12-C48S affects USP12
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2
USP12 affects mHTT-N586
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2
USP12 affects mHTT
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2
USP12 affects lipopolysaccharide
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2
USP12 activates lipopolysaccharide. 2 / 2
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2
USP12 affects cell growth
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1
1
USP12 affects angiogenesis
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2
USP12 inhibits angiogenesis.
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1
USP12 inhibits angiogenesis. 1 / 1
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1
USP12 activates angiogenesis.
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1
USP12 activates angiogenesis. 1 / 1
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1
USP12 affects Usp12-C48S
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2
USP12 affects Neoplasm Metastasis
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1
1
USP12 affects Neoplasm Invasiveness
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1
1
USP12 affects Interferon
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2
USP12 activates Interferon. 2 / 2
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2
USP12 affects Cell Survival
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1
1
USP12 inhibits Cell Survival.
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1
USP12 inhibits Cell Survival. 1 / 1
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1
USP12 activates Cell Survival.
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1
USP12 activates Cell Survival. 1 / 1
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1
USP12 affects Ang II-induced cardiac hypertrophy
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2
sparser
"Although the exact function of p80/Uaf1 in viral DNA replication remains unclear, this WD40 repeats-containing protein is known to interact with the de-ubiquitinating enzymes Usp1, Usp12 and Usp46, whose substrates include PCNA, histones H2A and H2B and Fanconi anaemia complementation group D type 2, a component of the Fanconi anaemia pathway [ xref , xref ]."
reach
"Consistently, ectopic expression of the myristoylated form of AKT1 (myr-AKT1) significantly repressed USP12 expression in both human and mouse tumour cells (Fig. 1k); knockdown of endogenous AKT1 or AKT2, the two major isoforms of AKT, induced higher levels of USP12 than did the control treatment (Fig. 1l)."
Β-propeller proteins affects USP12
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1
Vorinostat affects USP12
1
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Vincristine affects USP12
1
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1
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Transmitting long-range allosteric signal BL1 affects USP12
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1
Titanium dioxide affects USP12
1
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Testosterone affects USP12
1
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Substrate affinity affects USP12
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1
reach
"Treatment with inhibitors targeting MEK (U0126), ERK (ERK inhibitor), JNK (JNK inhibitor II), JAK-STAT3 (WP1066), c-Myc (c-Myc inhibitor), p38 MAPK (SB203580), and TGF-β-SMAD (SB431542 and SIS3) failed to produce a substantial change in USP12 expression (Supplementary Fig. 1e); however, blocking AKT-mTOR signalling using the selective AKT inhibitor API-2 or the mTOR inhibitor rapamycin significantly increased USP12 expression (Fig. 1i, j)."
Silicon dioxide affects USP12
1
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Potassium chromate affects USP12
1
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Pirimiphos-methyl affects USP12
1
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Phorbol 13-acetate 12-myristate affects USP12
1
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PcDNA3.1 affects USP12
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1
Optimizing catalytic cleft affects USP12
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1
Mutation Ub globular domain-binding residue BL1 affects USP12
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1
eidos
"Finally , consistent with the expected substrate-induced interactions between Ub and BL1 of USP12 in all forms , mutation of a Ub globular domain-binding residue on BL1 , Y264 , compromised the ability of both UAF1 and WDR20 to activate USP12 for Ub-AMC hydrolysis ( Figures 6D , 6E , and S5F ) ."
Medroxyprogesterone acetate affects USP12
1
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MTOR inhibitor affects USP12
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1
MTOR inhibitor decreases the amount of USP12. 1 / 1
|
1
reach
"Treatment with inhibitors targeting MEK (U0126), ERK (ERK inhibitor), JNK (JNK inhibitor II), JAK-STAT3 (WP1066), c-Myc (c-Myc inhibitor), p38 MAPK (SB203580), and TGF-β-SMAD (SB431542 and SIS3) failed to produce a substantial change in USP12 expression (Supplementary Fig. 1e); however, blocking AKT-mTOR signalling using the selective AKT inhibitor API-2 or the mTOR inhibitor rapamycin significantly increased USP12 expression (Fig. 1i, j)."
MHTT affects USP12
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1
Lipopolysaccharide affects USP12
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1
Lipopolysaccharide decreases the amount of USP12. 1 / 1
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1
Leflunomide affects USP12
1
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Hypochlorous acid affects USP12
1
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Hsa-miR-9500 affects USP12
1
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Hsa-miR-92a-2-5p affects USP12
1
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Hsa-miR-8083 affects USP12
1
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Hsa-miR-7515 affects USP12
1
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Hsa-miR-744-5p affects USP12
1
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Hsa-miR-7109-5p affects USP12
1
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Hsa-miR-6887-5p affects USP12
1
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Hsa-miR-6885-5p affects USP12
1
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Hsa-miR-6876-5p affects USP12
1
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Hsa-miR-6795-5p affects USP12
1
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Hsa-miR-6780b-5p affects USP12
1
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Hsa-miR-625-5p affects USP12
1
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Hsa-miR-5196-5p affects USP12
1
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Hsa-miR-4747-5p affects USP12
1
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Hsa-miR-4725-3p affects USP12
1
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Hsa-miR-4533 affects USP12
1
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Hsa-miR-4476 affects USP12
1
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Hsa-miR-4472 affects USP12
1
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Hsa-miR-4447 affects USP12
1
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Hsa-miR-4271 affects USP12
1
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Hsa-miR-373-3p affects USP12
1
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Hsa-miR-328-5p affects USP12
1
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Hsa-miR-3202 affects USP12
1
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Hsa-miR-215-5p affects USP12
1
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Hsa-miR-192-5p affects USP12
1
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Hsa-miR-1260b affects USP12
1
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Hsa-miR-1252-5p affects USP12
1
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Geldanamycin affects USP12
1
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Formaldehyde affects USP12
1
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Doxorubicin affects USP12
1
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Dicrotophos affects USP12
1
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Cre affects USP12
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1
Clofibrate affects USP12
1
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Bucladesine affects USP12
1
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Binding tip Fingers domain affects USP12
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1
Avobenzone affects USP12
1
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Aluminium atom affects USP12
1
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Aflatoxin M1 affects USP12
1
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Aflatoxin B1 affects USP12
1
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WD40-repeat-containing protein affects USP12
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1
eidos
"Highlights d Free USP12 deubiquitinase is inactive and has several flexible structural elements d UAF1 and WDR20 can both activate USP12 without increasing its substrate affinity d UAF1 and WDR20 bind USP12 at two distinct sites away from its catalytic center d Two distinct allosteric mechanisms underlie USP12 activation by UAF1 and WDR20 Ubiquitin-specific proteases ( USPs ) constitute the largest family of deubiquitinating enzymes , whose catalytic competency is often modulated by their binding partners through unknown mechanisms ."
USP12 affects tumour-promoting secretome resulting insufficient PPM1B deubiquitination
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1
USP12 affects tumor growth
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1
USP12 affects transduction
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1
USP12 inhibits transduction. 1 / 1
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1
reach
"Thus, USP12 and OTUD7B counterbalance inhibitory E3 ligases to stabilize TCR signaling.Aside from acting at the proximal signalosome, E3 ligases also inhibit T-cell activation by acting further downstream, controlling the key transduction events that lead to the nuclear translocation of the T-cell activating transcription factors."
| PMC
USP12 affects transcription downstream METTL3
|
1
USP12 affects protein stability cells
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1
USP12 affects polyubiquitination
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1
USP12 affects pcDNA3.1
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1
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1
USP12 activates negative regulation of apoptotic process. 1 / 1
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1
USP12 affects macrophage activation
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1
USP12 activates macrophage activation. 1 / 1
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1
USP12 affects lung tumour resistance PD-1
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1
USP12 affects lung metastasis 4T1 cells
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1
USP12 affects function monocytic MDSCs
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1
USP12 affects function M-MDSCs
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1
USP12 affects dephosphorylation TCPTP p-STAT1
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1
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1
USP12 inhibits cytokine-mediated signaling pathway. 1 / 1
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1
reach
"Gene ontology (GO) analysis revealed that the pathways significantly enriched in USP12-downregulated genes were mostly related to cytokine-mediated signalling pathway and immune effector process (Fig. 3a); further in-depth examination showed that USP12 expression decreased levels of a number of chemokine, such as CXCL8, CXCL1, CXCL2, CCL2 and CCL5, most of which were associated with immune cell recruitment (Fig. 3b and Supplementary Fig. 2a)."
USP12 affects cre
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1
USP12 affects clonogenicity
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1
USP12 affects chemokine production
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1
USP12 inhibits chemokine production. 1 / 1
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1
USP12 affects cellular senescence
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1
USP12 activates cellular senescence. 1 / 1
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1
USP12 affects breast cancer angiogenesis
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1
USP12 affects bortezomib
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1
USP12 activates bortezomib. 1 / 1
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1
USP12 affects WDR48.USP12 complex
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1
reach
"Our previous observations for the LNCaP cell line that express AR FL but not AR Vs have demonstrated that USP12 silencing causes a decrease in transcript expression of all the AR target genes [XREF_BIBR] supporting our data that AR Vs are not targeted by USP12 in the AR V expressing CWR22Rv1 cell line."
USP12 affects UAF1DeltaSLD
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1
USP12 affects UAF1DSLD
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1
USP12 affects T cell activation
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1
USP12 inhibits T cell activation. 1 / 1
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1
reach
"Thus, USP12 and OTUD7B counterbalance inhibitory E3 ligases to stabilize TCR signaling.Aside from acting at the proximal signalosome, E3 ligases also inhibit T-cell activation by acting further downstream, controlling the key transduction events that lead to the nuclear translocation of the T-cell activating transcription factors."
| PMC
USP12 affects Snail1
|
1
USP12 affects Sf9
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1
USP12 affects PHLPP1.WDR48
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1
USP12 affects Multiple Myeloma
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1
USP12 activates Multiple Myeloma. 1 / 1
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1
USP12 affects MDM2-P53
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1
USP12 affects M-MDSC
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1
USP12 affects LPS with O-antigen
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1
USP12 activates LPS with O-antigen. 1 / 1
|
1
USP12 affects ISG65
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1
USP12 affects HMGB1-mediated autophagy
|
1
USP12 affects H2BK120ub
|
1
USP12 affects H2AK119ub
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1
USP12 affects DNA replication
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1
USP12 inhibits DNA replication. 1 / 1
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1
USP12 affects Carcinogenesis
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1
USP12 activates Carcinogenesis. 1 / 1
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1
USP12 affects CREB-binding protein-induced acetylation p-STAT1
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1
USP12 affects CD4+
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1
USP12 affects CD4 T cell responses
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1
USP12 affects Angiotensin-2
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1
USP12 inhibits Angiotensin-2. 1 / 1
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1
USP12 affects Ang II-induced myocardial hypertrophy
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1
USP12 affects AKT-mTOR
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1
USP affects USP12
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1
sparser
"Highlights d Free USP12 deubiquitinase is inactive and has several flexible structural elements d UAF1 and WDR20 can both activate USP12 without increasing its substrate affinity d UAF1 and WDR20 bind USP12 at two distinct sites away from its catalytic center d Two distinct allosteric mechanisms underlie USP12 activation by UAF1 and WDR20
Ubiquitin-specific proteases (USPs) constitute the largest family of deubiquitinating enzymes, whose catalytic competency is often modulated by their binding partners through unknown mechanisms."
UAF1DeltaSLD affects USP12
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1
UAF1DSLD affects USP12
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1
Small hairpin affects USP12
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1
reach
"XREF_BIBR, XREF_BIBR In addition, other E3 ubiquitin ligases are probably involved in the AR regulation process, such as CHIP XREF_BIBR and SKP2 XREF_BIBR which also promote AR degradation, and Siah2, XREF_BIBR RNF6, XREF_BIBR and USP12 XREF_BIBR, XREF_BIBR which promote deubiquitination and AR activation."
reach
"XREF_BIBR, XREF_BIBR In addition, other E3 ubiquitin ligases are probably involved in the AR regulation process, such as CHIP XREF_BIBR and SKP2 XREF_BIBR which also promote AR degradation, and Siah2, XREF_BIBR RNF6, XREF_BIBR and USP12 XREF_BIBR, XREF_BIBR which promote deubiquitination and AR activation."
RNAi affects USP12
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1
eidos
"Highlights d Free USP12 deubiquitinase is inactive and has several flexible structural elements d UAF1 and WDR20 can both activate USP12 without increasing its substrate affinity d UAF1 and WDR20 bind USP12 at two distinct sites away from its catalytic center d Two distinct allosteric mechanisms underlie USP12 activation by UAF1 and WDR20 Ubiquitin-specific proteases ( USPs ) constitute the largest family of deubiquitinating enzymes , whose catalytic competency is often modulated by their binding partners through unknown mechanisms ."
PHLPP1.WDR48 affects USP12
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1
Figures affects USP12
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1
Figure affects USP12
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1
DEHP A2780 cells affects USP12
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1
1
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sparser
"Other examples of protein complexes retrieved include host cell factor-1, galectin 7, p97, ras GTPase binding proteins 1 and 2, WD-repeat containing protein 48 and WD-repeat containing protein 20, and thioredoxin like protein, which interact with BAP, USP1, ataxin-3, USP10, USP12, and USP14 or UCH-L5 [ xref , xref ], respectively."
reach
"Consistently, ectopic expression of the myristoylated form of AKT1 (myr-AKT1) significantly repressed USP12 expression in both human and mouse tumour cells (Fig. 1k); knockdown of endogenous AKT1 or AKT2, the two major isoforms of AKT, induced higher levels of USP12 than did the control treatment (Fig. 1l)."
reach
"Consistently, ectopic expression of the myristoylated form of AKT1 (myr-AKT1) significantly repressed USP12 expression in both human and mouse tumour cells (Fig. 1k); knockdown of endogenous AKT1 or AKT2, the two major isoforms of AKT, induced higher levels of USP12 than did the control treatment (Fig. 1l)."
1
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1
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17beta-estradiol affects USP12
1
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4,4'-diaminodiphenylmethane affects USP12
1
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