https://transhumanist.ru/index.php?action=history&feed=atom&title=BAP1BAP1 - История изменений2026-06-15T06:38:16ZИстория изменений этой страницы в викиMediaWiki 1.43.6https://transhumanist.ru/index.php?title=BAP1&diff=5973&oldid=prevOdysseusBot: Новая страница: «Ubiquitin carboxyl-terminal hydrolase BAP1 (EC 3.4.19.12) (BRCA1-associated protein 1) (Cerebral protein 6) [KIAA0272] [hucep-6] ==Publications== {{medline-entr...»2021-05-12T15:03:18Z<p>Новая страница: «Ubiquitin carboxyl-terminal hydrolase BAP1 (EC 3.4.19.12) (BRCA1-associated protein 1) (Cerebral protein 6) [KIAA0272] [hucep-6] ==Publications== {{medline-entr...»</p>
<p><b>Новая страница</b></p><div>Ubiquitin carboxyl-terminal hydrolase BAP1 (EC 3.4.19.12) (BRCA1-associated protein 1) (Cerebral protein 6) [KIAA0272] [hucep-6]<br />
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==Publications==<br />
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{{medline-entry<br />
|title=The [[BAP1]]/[[ASXL2]] Histone H2A Deubiquitinase Complex Regulates Cell Proliferation and Is Disrupted in Cancer.<br />
|pubmed-url=https://pubmed.ncbi.nlm.nih.gov/26416890<br />
|abstract=The deubiquitinase (DUB) and tumor suppressor [[BAP1]] catalyzes ubiquitin removal from histone H2A Lys-119 and coordinates cell proliferation, but how [[BAP1]] partners modulate its function remains poorly understood. Here, we report that [[BAP1]] forms two mutually exclusive complexes with the transcriptional regulators [[ASXL1]] and [[ASXL2]], which are necessary for maintaining proper protein levels of this DUB. Conversely, [[BAP1]] is essential for maintaining [[ASXL2]], but not [[ASXL1]], protein stability. Notably, cancer-associated loss of [[BAP1]] expression results in [[ASXL2]] destabilization and hence loss of its function. [[ASXL1]] and [[ASXL2]] use their ASXM domains to interact with the C-terminal domain (CTD) of [[BAP1]], and these interactions are required for ubiquitin binding and H2A deubiquitination. The deubiquitination-promoting effect of ASXM requires intramolecular interactions between catalytic and non-catalytic domains of [[BAP1]], which generate a composite ubiquitin-binding interface (CUBI). Notably, the CUBI engages multiple interactions with ubiquitin involving (i) the ubiquitin carboxyl hydrolase catalytic domain of [[BAP1]], which interacts with the hydrophobic patch of ubiquitin, and (ii) the CTD domain, which interacts with a charged patch of ubiquitin. Significantly, we identified cancer-associated mutations of [[BAP1]] that disrupt the CUBI and notably an in-frame deletion in the CTD that inhibits its interaction with [[ASXL1]]/2 and DUB activity and deregulates cell proliferation. Moreover, we demonstrated that [[BAP1]] interaction with [[ASXL2]] regulates cell senescence and that [[ASXL2]] cancer-associated mutations disrupt [[BAP1]] DUB activity. Thus, inactivation of the [[BAP1]]/[[ASXL2]] axis might contribute to cancer development. <br />
|mesh-terms=* Cell Proliferation<br />
* HEK293 Cells<br />
* HeLa Cells<br />
* Histones<br />
* Humans<br />
* Multiprotein Complexes<br />
* Neoplasms<br />
* Repressor Proteins<br />
* Tumor Suppressor Proteins<br />
* Ubiquitin Thiolesterase<br />
* Ubiquitin-Specific Proteases<br />
|keywords=* ASXL<br />
* BAP1<br />
* Calypso<br />
* Polycomb Group Proteins<br />
* cancer biology<br />
* cell proliferation<br />
* cellular senescence<br />
* deubiquitylation (deubiquitination)<br />
* epigenetics<br />
* histone H2A ubiquitination<br />
|full-text-url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4661380<br />
}}</div>OdysseusBot