IndraLab

Statements

OTUB1 activates TP53. 25 / 33
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"Through deubiquitination, OTUB1 promotes the stability of p53, thereby enhancing its tumor suppressor activity."
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"Monoubiquitination of OTUB1, primarily at lysines 59 and 109, is critical for OTUB1 function to suppress UbcH5 and induce p53, and the DUB activity of Ataxin-3 and JOSD1 can be enhanced through ubiquitination of lysine 117 on Ataxin-3 and lysine 136 on JOSD1."
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"OTUB1 promotes p53 stabilization and also functions as a negative regulator of RNF168 dependent ubiquitylation at sites of DNA damage [XREF_BIBR, XREF_BIBR]."
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"In addition, cathepsin K inhibition also increases Bax mRNA and protein expression via OTUB1-mediated p53 stabilization [13]."
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"OTUB1 directly suppresses MDM2-mediated p53 ubiquitination, and overexpression of OTUB1 leads to stabilization and activation of p53 ( Sun et al., 2012 )."
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"Inhibition of cathepsin K sensitizes oxaliplatin-induced apoptotic cell death by Bax upregulation through OTUB1-mediated p53 stabilization in vitro and in vivo."
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"Doxycycline induced expression of Otub1 in T-Rex-U2OS-Flag-Otub1 cells also drastically induced the levels of MDMX, as well as p53 and its target MDM2 in a time dependent manner."
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"Interestingly, Otub1 abrogates p53 ubiquitination and stabilizes and activates p53 in cells independently of its deubiquitinating enzyme activity."
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"As described in our previous work, Otub1 stabilizes and activates p53 and can induce apoptosis [ xref ]."
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"Consequently, overexpression of Otub1 induces p53 dependent apoptosis and inhibition of cell proliferation whereas knockdown of Otub1 attenuates p53 activation following DNA damage [XREF_BIBR]."
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"In summary, we have found that Otub1 promotes p53 function by stabilizing MDMX, which in turn contributes to the p53 induced mitochondria mediated apoptosis pathway."
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"This non canonical mode of regulation was also reported when OTUB1 was shown to stabilize and activate p53 independent of catalytic activity [XREF_BIBR]."
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"Interestingly, OTUB1 was recently shown to modulate p53 stability through inhibition of UbcH5."
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"Diego Iglesias-Gato et al. found that OTUB1 promotes the invasion and tumorigenesis of prostate cancer in vitro and in vivo by mediating Rho-A and P53 [ 47 ]."
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"For example, USP7 regulates the stability of both p53 and Mdm2 and maintains p53 ubiquitination levels; xref USP2 mediates the stability of Mdm2; xref USP10 modulates p53 localization and stability; xref OTUB1 abrogates p53 ubiquitination and activates p53. xref Interestingly, USP10 can stabilize both mutated and wild-type p53, with a dual role in tumorigenesis."
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"OTUB1 is overexpressed in certain human cancers and has been demonstrated to inhibit TP53 degradation via modulating the activities of MDM2 and MDMX, which results in apoptosis [ 154 ]."
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"OTUB1 modulates p53 stability by suppressing the conjugation between MDM2 and its E2 enzyme, UbcH5."
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"Overexpression of OTUB1 induces p53 dependent apoptosis whereas its knockdown attenuates p53 activation."
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"It has been known that OTUB1 can remove ubiquitin or polyubiquitin from p53 and increase the stability of p53 ."
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"In response to DNA-damaging agents, OTUB1 can stabilize and activate p53, leading to the inhibition of cell proliferation and apoptosis. xref , xref However, p53 expression and function is commonly lost during tumourigenesis and thus, the role of OTUB1 in the subsequent breast cancer progression and drug resistance will not be clear-cut. xref , xref "
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"Casein kinase 2 (CK2)-dependent phosphorylation of OTUB1 at Ser16 played a critical role in ODN- and cathepsin K siRNA-mediated p53 stabilization."
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"Mitochondrial ROS scavengers prevented OTUB1-mediated p53 stabilization and Bax upregulation by ODN."
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"Our results demonstrate that cathepsin K inhibition enhances oxaliplatin-induced apoptosis by increasing OTUB1 phosphorylation via CK2 activation, thereby promoting p53 stabilization, and hence upregulating Bax."
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"Silencing of OTUB1 suppressed the upregulation of p53 caused by ASPP1 knockdown (Fig. 6d)."
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"For example, USP7 modulates the stability of both p53 and MDM2, and maintains the level of p53 ubiquitylation ( xref , xref ); USP2 affects the stability of MDM2 ( xref ); Otub1 inhibits p53 ubiquitination and activates p53 in cells ( xref ); USP10 regulates the location and stability of p53, and stabilize both mutated and wild-type p53, thereby having a dual role in tumorigenesis ( xref )."
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