Редактирование: ASXL2 (раздел)

==Publications==

{{medline-entry
|title=Genomewide meta-analysis identifies loci associated with IGF-I and IGFBP-3 levels with impact on age-related traits.
|pubmed-url=https://pubmed.ncbi.nlm.nih.gov/27329260
|abstract=The growth hormone/insulin-like growth factor (IGF) axis can be manipulated in animal models to promote longevity, and IGF-related proteins including IGF-I and IGF-binding protein-3 (IGFBP-3) have also been implicated in risk of human diseases including cardiovascular diseases, diabetes, and cancer. Through genomewide association study of up to 30 884 adults of European ancestry from 21 studies, we confirmed and extended the list of previously identified loci associated with circulating IGF-I and IGFBP-3 concentrations (IGF1, [[IGFBP3]], [[GCKR]], [[TNS3]], [[GHSR]], [[FOXO3]], [[ASXL2]], [[NUBP2]]/IGFALS, [[SORCS2]], and [[CELSR2]]). Significant sex interactions, which were characterized by different genotype-phenotype associations between men and women, were found only for associations of IGFBP-3 concentrations with SNPs at the loci [[IGFBP3]] and [[SORCS2]]. Analyses of SNPs, gene expression, and protein levels suggested that interplay between [[IGFBP3]] and genes within the [[NUBP2]] locus (IGFALS and HAGH) may affect circulating IGF-I and IGFBP-3 concentrations. The IGF-I-decreasing allele of SNP rs934073, which is an eQTL of [[ASXL2]], was associated with lower adiposity and higher likelihood of survival beyond 90 years. The known longevity-associated variant rs2153960 ([[FOXO3]]) was observed to be a genomewide significant SNP for IGF-I concentrations. Bioinformatics analysis suggested enrichment of putative regulatory elements among these IGF-I- and IGFBP-3-associated loci, particularly of rs646776 at [[CELSR2]]. In conclusion, this study identified several loci associated with circulating IGF-I and IGFBP-3 concentrations and provides clues to the potential role of the IGF axis in mediating effects of known ([[FOXO3]]) and novel ([[ASXL2]]) longevity-associated loci. 
|mesh-terms=* Adult
* Aging
* Female
* Gene Expression Regulation
* Genome-Wide Association Study
* Humans
* Insulin-Like Growth Factor Binding Protein 3
* Insulin-Like Growth Factor I
* Male
* Metabolome
* Quantitative Trait Loci
* Quantitative Trait, Heritable
* Regulatory Sequences, Nucleic Acid
|keywords=* IGF-I
* IGFBP-3
* aging
* genomewide association study
* growth hormone axis
* longevity
|full-text-url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5013013
}}
{{medline-entry
|title=The [[BAP1]]/[[ASXL2]] Histone H2A Deubiquitinase Complex Regulates Cell Proliferation and Is Disrupted in Cancer.
|pubmed-url=https://pubmed.ncbi.nlm.nih.gov/26416890
|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. 
|mesh-terms=* Cell Proliferation
* HEK293 Cells
* HeLa Cells
* Histones
* Humans
* Multiprotein Complexes
* Neoplasms
* Repressor Proteins
* Tumor Suppressor Proteins
* Ubiquitin Thiolesterase
* Ubiquitin-Specific Proteases
|keywords=* ASXL
* BAP1
* Calypso
* Polycomb Group Proteins
* cancer biology
* cell proliferation
* cellular senescence
* deubiquitylation (deubiquitination)
* epigenetics
* histone H2A ubiquitination
|full-text-url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4661380
}}