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Ubiquitin binds USP14. 29 / 29
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sparser
"When Usp14 binds a substrate or Ub aldehyde, the orientation of its C-terminal region undergoes changes in its structure ( xref ; xref )."
20005843
sparser
"Structural and biochemical data pointed that IU1 and its analogs bind competitively with the ubiquitin C-terminus to the catalytic active site of USP14 through a previously unknown steric blockade mechanism."
35069211
sparser
"Gate opening occurs following the association of proteasome-associated USP14 with ubiquitin conjugates ( Peth et al., 2009 ), supporting the idea that deubiquitination and degradation are dynamic even[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"
22819849
sparser
"Comparison of the crystal structures for the free and Ub bound catalytic core domain of USP14 suggests that the enzyme is activated by conformational translocation of two enzyme surface loops, which block access of the Ub C-terminus to the active site in the free enzyme ( xref )."
17291557
sparser
"In the USP14/ubiquitin-aldehyde complex, where the ubiquitin C terminus is covalently bound to the site cysteine and only one C-terminal oxygen is present, Asn108 (Asn218 in USP2) interacts with the h[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"
16905103
sparser
"They found that the conformation of the Ub β1–β2 loop is important for the Ub binding to USP14."
27501351
sparser
"Inhibition of USP14 induces the K63-linked ubiquitination of PRV VP16, where USP14 directly binds to ubiquitin chains on VP16 through its UBL domain during the early stage of viral infection."
35336954
sparser
"It is also a reversible non‐selective competitive inhibitor of USP14, targeting the formation of Ub‐USP14 or Ub‐UCHL5 conjugates. xref  This is achieved by inhibiting the enzymatic activity of USP14 and UCHL5, and VLX1570 shows significant anti‐cancer impact in multiple myeloma and Waldenstrom's macroglobulinemia. xref Anchored in these findings, a phase 1/2 trial evaluating the efficacy and tolerability of VLX1570 in patients with relapsed or refractory multiple myeloma is currently under way (NCT02372240). xref "
34854221
sparser
"Further study will be required to determine if proteasome-bound USP14 can interact with K63-linked ubiquitin chains or, alternatively, whether USP14’s DUB activity can be stimulated by a novel binding partner, allowing it to be active when not bound to the proteasome."
25575639
sparser
"Usp14 binds ubiquitin using its Fingers domain and a binding groove between the Palm and Thumb domains."
28988953
sparser
"Because the UBL, by itself, alters the activity of the ATPases in a similar manner as does the binding of a ubiquitin chain or ubiquitin aldehyde to Usp14 [ xref ], it is very likely that the proteasome activation upon substrate binding to Usp14 is mediated by its UBL domain."
34067263
sparser
"Here, we compare the structure of the PL pro -Ub complex with those of the USP2-Ub (PDB entry 2hd5; Renatus et al., 2006) , USP14-Ub aldehyde (PDB entry 2ayo; Hu et al., 2005) and HAUSP-Ub aldehyde (PDB entry 1nbf; Hu et al., 2002) complexes ( Supplementary Fig. S6 )."
24531491
sparser
"Only approximately 1000 Å 2 of the surface area of PL pro (640 Å 2 by the Ub core and 360 Å 2 by the Ub C-terminus) is buried in the interface, which is smaller than in the USP2-Ub (1900 Å 2 ; Supplementary Fig. S6b ), USP14-Ub aldehyde (1500 Å 2 ; Supplementary Fig. S6c ) and HAUSP-Ub aldehyde (1700 Å 2 ) complexes."
24531491
sparser
"Usp14’s N -terminal ubiquitin-like domain (UBL) docks onto the proteasome through interacting with Rpn-1’s T2 domain.[ xref ][ xref , xref ][ xref , xref ][ xref , xref ][ xref , xref ][ xref , xref ][ xref , xref ][ xref , xref ][ xref , xref ]A 2016 cryo-EM structure at 4.35 Å resolution was solved of the 26S proteasome bound to the Usp14-ubiquitin aldehyde complex (UbAl, a covalent inhibitor of Usp14 where the C -terminal carboxylate is replaced with an aldehyde), xref .[ xref ]It displayed Usp14’s proximity to Rpn-1 (although the UBL domain appeared to have no density due to its flexibility), and Rpn-1’s position in the 19S RP was observed to undergo the most movement (50-60 Å) when bound to Usp14.[ xref ]While the UBL domain interacts with Rpn-1, Usp14 also interacts with Rpt-1 and Rpt-2 oligosacharide-binding domains to further help dock itself onto the proteasome."
30740849
sparser
"A H426A mutation may abolish this H bond and abrogate the interaction between Ub and USP14 (Supplementary information, Fig.  xref )."
30254335
sparser
"Undoubtedly, DUB activity is a promising strategy for cancer therapy. xref  VLX1570 targets the Ub‐USP14 or Ub‐UCHL5 conjugates and is a reversible non‐selective competitive inhibitor of ubiquitin peptidase 14 (USP14) and ubiquitin carboxyl‐terminal hydrolase 5 (UCHL5) in multiple myeloma. xref  VLX1570 has been shown to have significant anti‐cancer efficacy with high potency and solubility."
34854221
sparser
"To assess the interaction of USP14 with cellular ubiquitin pools, we performed immunoblot analysis on spinal cord extracts from wild type, Tg CA , andax J mice (Figure xref )."
25954152
reach
"They found that the conformation of the Ub beta1-beta2 loop is important for the Ub binding to USP14."
27501351
sparser
"Consequently, boththese Y476 mutants could not form complex with Ub-PA, and the D199A mutant also abolished the interaction between USP14 and Ub-PA (Supplementary information, Fig.  xref )."
30254335
sparser
"The results showed that IU1 exerted its inhibitory activity by binding to the thumb-palm cleft region of the USP14 catalytic domain, which prevented the binding of the C-terminus of ubiquitin to USP14 via steric blockade."
30254335
sparser
"We observed that at a 5 mM concentration IU1 significantly inhibited the formation of the USP14/Ub-PA complex (Fig.  xref ), which is in good agreement with the proposed steric blockade mechanism (vide infra)."
30254335
sparser
"Not all functions of USP14 at the proteasome depend on its catalytic activity: binding of USP14 to poly-Ub chains and unfolded peptides results in opening of the gates of the 20S proteasome and stimulation of the ATPase activity of the proteasome (Peth et al., xref , xref , xref )."
25191222
sparser
"Comparison of the crystal structures for the free and Ub bound catalytic core domain of USP14 suggests that the enzyme is activated by conformational translocation of two enzyme surface loops, which block access of the Ub C-terminus to the active site in the free enzyme (Hu et al., 2005)."
17291557
sparser
"USP14 directly bound to ubiquitin chains on VP16 through its UBL domain during the early stage of viral infection."
34822318
sparser
"The high-resolution co-crystal structures of USP14 (PDB ID: IU1, 6IIK; IU1-47, 6IIL) revealed that IU1 and its analogs bind competitively with the C-terminus of ubiquitin to the active site of USP14, thereby abrogating the catalytical activity of USP14 [ xref ]."
33925279
sparser
"However, we found that all the three OBs only partially inhibited the ubiquitin-binding activity of USP14 ( xref , bottom panel, lanes 5–8)."
30963630
sparser
"Y476 may maintain the ideal architecture of the catalytic center for Ub binding via the formation of an H bond with D199 in USP14 (Supplementary information, Fig.  xref )."
30254335
sparser
"USP14 is reversely associated with the proteasome to trim K48 Ub chains and negatively regulates proteasome activity ( xref )."
28029679
sparser
"The co-crystal structures of USP14 with IU1 showed that IU1 can bind to the thumb-palm cleft region of the USP14 catalytic domain, resulting in steric blockade of the binding of the ubiquitin C-terminus to USP14 [ xref , xref ]."
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