Additional Sex Comb-like 1 (ASXL1), in Cooperation with SRC-1, Acts as a Ligand-dependent Coactivator for Retinoic Acid Receptor

Cho, Yang-Sook; Kim, Eun-Joo; Park, Ui-Hyun; Sin, Hong‐Sig; Um, Soo‐Jong

doi:10.1074/jbc.m512616200

Cited by 132 publications

(124 citation statements)

References 49 publications

(46 reference statements)

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“…BAP1 was also shown to deubiquitinate and stabilize some of its interacting partners, including HCF-1 and OGT indicating the functional importance of its catalytic activity (19,22,23). ASXL1/2 contain two uncharacterized N-terminal domains, ASXN and ASXM, and a C-terminal plant homeodomain finger (36,41). Interestingly, the DUB activity of a BAP1 family member, UCH37, is stimulated by RPN13 (ADRM1) 19S proteasome subunit (42)(43)(44), and phylogenetic studies suggest that RPN13 and ASXL1/2 share a conserved domain termed the DEUBiquitinase ADaptor (DEUBAD) domain corresponding to ASXM (45).…”

mentioning

confidence: 99%

The BAP1/ASXL2 Histone H2A Deubiquitinase Complex Regulates Cell Proliferation and Is Disrupted in Cancer

Daou

Hammond-Martel

Mashtalir

et al. 2015

Journal of Biological Chemistry

104

121

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Background:The relevance of ASXL2 to the function of the histone H2A deubiquitinase BAP1 remains unknown. Results: ASXL2 promotes the assembly by BAP1 of a composite ubiquitin-binding interface (CUBI) required for DUB activity and coordination of cell proliferation. Conclusion: Cancer-associated mutations of BAP1 disrupt BAP1-ASXL2 interaction and function. Significance: We provide novel insights into BAP1 tumor suppressor function.

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confidence: 99%

The BAP1/ASXL2 Histone H2A Deubiquitinase Complex Regulates Cell Proliferation and Is Disrupted in Cancer

Daou

Hammond-Martel

Mashtalir

et al. 2015

Journal of Biological Chemistry

104

121

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“…For example, ASXL1 can interact with retinoic acid receptor in the presence of retinoic acid and enhance the transcription of some genes while repressing that of others, depending on the cell context. 15 The fine details of the mechanism of action of ASXL1 are not well defined yet, but the protein is involved in distinct multiprotein complexes that bind to and modify chromatin at target gene regions. Scheuermann et al demonstrated that ASXL1 exists in a complex, named polycomb repressive deubiquitinase, with BAP1, a ubiquitin carboxy-terminal hydrolase that removes monoubiquitin from histone 2A in nucleosomes.…”

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confidence: 99%

Epigenetics and mutations in chronic myeloproliferative neoplasms

Vannucchi¹,

Biamonte²

2011

Haematologica

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T he BCR-ABL1-negative classic myeloproliferative neoplasms, polycythemia vera (PV), essential thrombocytemia (ET) and primary myelofibrosis are clonal stem cell disorders associated with an increased production of mature blood cells belonging preferentially to one cell linage.1 They share substantial phenotypic mimicry, can undergo phenotypic shifts (from PV to ET and vice versa) as well as evolution to myelofibrosis (post-PV/post-ET myelofibrosis), and all eventually progress to leukemia. The hypothesis that hypersensitivity of hematopoietic stem and progenitor cells to cytokines might largely account for the pathogenesis of myeloproliferative neoplasms has been corroborated by the discovery of mutations that affect cytoplasmic proteins involved in cytokine signaling, either resulting in a gain-of-function (JAK2 and MPL) or a loss-of-function (CBL and LNK). Dysregulation of tyrosine kinases is a recurrent theme in chronic myeloid neoplasms, as exemplified by the constitutive activation of ABL caused by oligomerization of the BCR-ABL fusion protein in chronic myelogenous leukemia, the gain-of-function mutation of the tyrosine kinase receptor c-KIT in mastocytosis, and the activation of platelet-derived growth factor receptor-α or -b and fibroblast growth factor receptor in hypereosinophilic disorders. However, high-throughput genomic analyses of myeloproliferative neoplasms have recently identified a second group of mutations that affect proteins involved in the epigenetic regulation of transcription, such as TET2, ASXL1 and EZH2.2 These abnormalities can occur in association and/or with mutations targeting tyrosine kinases. (5mC) to 5-hydroxymethylcytosines (5hmC). EZH2 is the catalytic subunit of the PRC2 complex and trimethylates Lys-27 of histone H3 (H3K27) leading to transcriptional repression of target genes. ASXL1 exists in chromatin-associated multiprotein complexes, together with PcG and TrxG proteins, involved in modifications of chromatin configuration that result in repressed and enhanced transcription, respectively, in a cellular context-specific manner. Described loss-of-function mutations of EZH2, TET2 and ASXL1 presumably lead to suppression of catalytic activity of these enzymes. Mutant JAK2, but not the wild-type protein, phosphorylates protein arginine methyltransferase 5 (PRMT5), causing inhibition of its arginine methyltransferase activity on H2A and H4 (H2AR3me and H4R3me). JAK2 also phosphorylates Tyr 41 (Y41) on histone H3 leading to decreased HP1α binding to chromatin; the displacement of HP1α is magnified after enhanced H3Y41 phosphorylation due to JAK2V617F.

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“…The primers used were (forward) 5 0 -GGGAGATTGGTTCAATGTCC-3 0 and (reverse) 5 0 -CCTGGAGCACCTAGACACCC-3 0 . For specificity, a primer set encompassing RAR response element in p21WAF1 promoter was used as described (Cho et al, 2006).…”

Section: Wb and Ip Analysismentioning

confidence: 99%

“…After 24 h, the cells were treated with 2.5 mg/ml cisplatin (Amersham Pharmacia Biotech). The effect of cisplatin on cell growth was monitored by MTT (Sigma) assay as described earlier (Cho et al, 2006). For apoptosis assay, H1299 cells were transiently transfected with p53, p73a, AMPKa2 alone and together for 2 days.…”

Section: Mtt and Apoptosis Assaymentioning

confidence: 99%

Kinase activity-independent suppression of p73α by AMP-activated kinase α (AMPKα)

et al. 2008

Oncogene

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Although p73a induces many of the same cellular events as p53, it is structurally distinct from p53 in that it possesses a unique COOH-terminal domain. To dissect the function of this domain, we performed yeast twohybrid screening of a HeLa cDNA library using residues 552-636 of p73a as bait. Among the clones that showed a specific interaction with p73a was AMP-activated protein kinase a (AMPKa). Additional yeast two-hybrid assays indicated that the bc-binding domain of AMPKa is critical for the interaction with p73a. The interaction was further confirmed in vitro by glutathione S-transferase pull-down, and in vivo by immunoprecipitation and immunofluorescence microscopy. Transient coexpression of AMPKa resulted in downregulation of the effect of p73a, but not of p53, on various p53-responsive promoters. Chromatin immunoprecipitation indicated p73a-dependent recruitment of AMPKa to the p21WAF1 promoter. Treatment with 5-aminoimidazole-4-carboxamide ribonucleotide, an agonist of AMPKa, and expression of dominant-negative versions of AMPKa revealed that the repression of p73a was independent of AMPKa kinase activity. In addition, cisplatin-induced growth repression was impaired when AMPKa was overexpressed. Upon the knock down of AMPKa by siRNA, the induction of p21WAF1 by p73a was significantly increased. Taken together, these data indicate that AMPKa specifically regulates p73a by a direct interaction without affecting its phosphorylation status. From these data, we speculate that AMPKa may provide a molecular clue to understand the repressive role of the C-terminus of p73a in transcription and DNA damage response.

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Additional Sex Comb-like 1 (ASXL1), in Cooperation with SRC-1, Acts as a Ligand-dependent Coactivator for Retinoic Acid Receptor

Cited by 132 publications

References 49 publications

The BAP1/ASXL2 Histone H2A Deubiquitinase Complex Regulates Cell Proliferation and Is Disrupted in Cancer

The BAP1/ASXL2 Histone H2A Deubiquitinase Complex Regulates Cell Proliferation and Is Disrupted in Cancer

Epigenetics and mutations in chronic myeloproliferative neoplasms

Kinase activity-independent suppression of p73α by AMP-activated kinase α (AMPKα)

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