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HACE1 ubiquitinates RAC1. 42 / 44
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"We found that UbcH7, as well as E1 and ATP were all required for Rac1 ubiquitylation by HACE1, thereby establishing the ability of HACE1 to catalyze Rac1 ubiquitylation."
22036506
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"It is conceivable that phosphorylation of Ser 385 reduces the pool of active HACE1 at the membrane where Rac1 ubiquitination by HACE1 occurs 3."
29362425
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"The E3 ubiquitin ligase HACE1 is a potent tumor suppressor that controls cell proliferation and ubiquitylates the small GTPase Rac1 to target it to proteasomal degradation."
28317937
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"Oxygen sensor FIH inhibits HACE1 dependent ubiquitination of Rac1 to enhance metastatic potential in breast cancer cells."
30659265
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"Altogether, these data showed that Rac1 ubiquitylation by HACE1 is tuned by ECM stiffness via modulation of OPTN levels."
36229487
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"Importantly, we observed that ubiquitylation of Rac1 by HACE1 depends on Rac1 activation state."
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"Under hypoxic conditions, HACE1 is less hydroxylated due to the inactivation of FIH, and subsequently functions to ubiquitinate the active form of Rac1, leading to the proteasomal degradation of Rac1."
30659265
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"The focal distribution of mutants in ANK 5 and 6 together with the present study suggest that this region is of critical importance in the mechanism that link HACE1 ubiquitylation of Rac1 to its control of cell proliferation."
28317937
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"Importantly, we observed that ubiquitylation of Rac1 by HACE1 depends on Rac1 activation state."
22036506
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"HACE1 ubiquitinates GTP-bound RAC1 and causes its degradation [ xref ]."
27653971
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"E3 ligases HACE1, XIAP, and SCF/FBX19 ubiquitylate Rac1, resulting in its degradation and suppressing lamellipodial protrusions."
31965002
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"Nrf2 is a transcription factor for Hace1 (HECT domain and ankyrin repeat containing E3 ubiquitin protein ligase 1), and Hace1 binds and ubiquitylates Rac1 when the latter is associated with NADPH oxidase, thus blocking ROS generation by NOX [ xref , xref ]."
25649831
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"XREF_BIBR Conversely, Rac1 can be ubiquitylated by the E3 ligase HACE1, resulting in its proteasomal degradation, reducing Rac1 mediated migration."
27104658
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"The tumor suppressor HACE1 (HECT domain and Ankyrin repeat Containing E3 ubiquitin protein ligase 1) ubiquitinates and degrades active Rac1 thereby controlling Rac1 dependent NADPH oxidase activation."
26436133
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"It is interesting to note that HACE1 ubiquitylates Rac1 on Lys147 xref , which is remote from the regions that are structurally sensitive to the bound nucleotide; furthermore, this residue is fully accessible in inactive Rac1 bound to RhoGDI xref ."
28317937
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"An increase of ECM stiffness leads to elevation in the protein level of Optineurin, a HACE1 partner, which then stimulates Hace1-dependent ubiquitylation of Rac1."
36229487
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"Moreover, in breast cancer, HACE1 ubiquitinates and promotes the degradation of Rac1, then leading to impaired Rac signaling [XREF_BIBR]."
27213432
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"We first confirmed that Rac1 is ubiquitylated by Hace1 in our system by re-expressing Hace1 in Hace1-/- MEFs (XREF_FIG), consistent with previous findings XREF_BIBR XREF_BIBR."
23864022
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"Indeed, siRNA mediated NOXA1 knockdown completely blocked Hace1 ubiquitylation of Rac1 (XREF_FIG), indicating that Hace1 preferentially targets NOXA1 associated Rac1."
23864022
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"Ubiquitylation of active Rac1 by the E3 Ubiquitin-Ligase HACE1."
22790197
sparser
"Indeed, siRNA-mediated NOXA1 knockdown completely blocked Hace1 ubiquitylation of Rac1 ( xref ), indicating that Hace1 preferentially targets NOXA1-associated Rac1."
23864022
sparser
"Our work identifies a role of OPTN in integrin mechanotransduction via modulation of HACE1 E3 ligase-mediated ubiquitylation of Rac1 in response to ECM rigidity and via force transmission by integrins."
36229487
sparser
"The focal distribution of mutants in ANK 5 and 6 together with the present study suggest that this region is of critical importance in the mechanism that link HACE1 ubiquitylation of Rac1 to its control of cell proliferation."
28317937
signor
"The CNF1 toxin of pathogenic Escherichia coli addresses Rac1 to ubiquitin-proteasome system (UPS). We report the essential role of the tumor suppressor HACE1, a HECT-domain containing E3 ubiquitin-ligase, in the targeting of Rac1 to UPS. HACE1 binds preferentially GTP-bound Rac1 and catalyzes its polyubiquitylation"
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"As a consequence of its permanent activation, Rac1 gets ubiquitinated by HACE1 and is subsequently targeted by the 26S proteasome degradation machinery XREF_BIBR, XREF_BIBR."
29362425
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"The E3 Ubiquitin-Ligase HACE1 907 Catalyzes the Ubiquitylation of Active Rac1."
| DOI
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"HACE1 expression increases the ubiquitination of Rac1 when the GTPase is activated."
34707697
sparser
"In response to cytotoxic necrotizing factor-1 or hepatocyte growth factor, Hace1 ubiquitylates and targets GTP-bound (activated) Rac1 for proteosomal degradation to block Rac1-dependent bacterial invasion ( xref ) and cell migration ( xref ), respectively."
25284589
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"Moreover, in breast cancer, HACE1 ubiquitinates and promotes the degradation of Rac1, then leading to impaired Rac signaling [29]."
27213432
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"For instance, inhibitors of HACE1 or HUWE1 significantly decreased ubiquitination of the HACE1 target Rac1 or stabilized the protein levels of HUWE1 and its substrate c-Myc, respectively."
26949039
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"Mechanistically, we show that Hace1 binds and ubiquitinates Rac1 when the latter associates with the complex through Noxa1."
23864022
sparser
"We found that UbcH7, as well as E1 and ATP were all required for Rac1 ubiquitylation by HACE1, thereby establishing the ability of HACE1 to catalyze Rac1 ubiquitylation ( Figure 2 A and Figure S2 A)[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"
22036506
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"HACE1 negatively regulates neuroinflammation through ubiquitylating and degrading Rac1 in Parkinson's disease models."
34593974
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"These data thus provide molecular evidence that the ubiquitylation of Rac1 by HACE1 is controlled by guanine nucleotide bound state of Rac1."
22036506
sparser
"Indeed, a recent study has shown that the tumor suppressor HACE1, an E3 ubiquitin-ligase, binds preferentially GTP-bound Rac1 and increases the ubiquitylation of active Rac1, leading to the decrease in cellular levels of GTP-bound Rac1 [ xref ]."
26588713
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"For instance, inhibitors of HACE1 or HUWE1 significantly decreased ubiquitination of the HACE1 target Rac1 (XREF_SUPPLEMENTARY) or stabilized the protein levels of HUWE1 and its substrate c-Myc, respectively (XREF_SUPPLEMENTARY)."
26949039
sparser
"These data thus provide molecular evidence that the ubiquitylation of Rac1 by HACE1 is controlled by guanine nucleotide-bound state of Rac1."
22036506
sparser
"Here we show that Hace1 binds and ubiquitylates Rac1 when the latter is associated with NOXA1 at the NADPH oxidase complex, thus blocking ROS generation by the complex."
23864022
sparser
"Our study of the functional interplay between HACE1 and Rac1 in cancer thus sheds a new light on the molecular mechanism of Rac1 ubiquitylation by HACE1 and the impact of its cancer-associated mutations in cell proliferation."
28317937
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"We and others have shown that HACE1 ubiquitinates Rac1 once it is activated, either by using point mutants (Q61L, Q61E, and G12V), by over-expressing the GEF domain of Dbl, or in response to growth factors such as Hepatocyte Growth Factor (HGF), Epidermal Growth Factor (EGF) and Heregulin (HRG) XREF_BIBR, XREF_BIBR, XREF_BIBR."
29362425
sparser
"To validate this we analyzed whether NOXA1 is required for Rac1 ubiquitylation by Hace1."
23864022
ubibrowser
"UbiNet 2.0"
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