Functional and cancer genomics of ASXL family members.
Functional and cancer genomics of ASXL family members.
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DOI：
10.1038/bjc.2013.281
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发表时间：
2013-07-23
影响因子：
8.8
通讯作者：
Katoh M
中科院分区：
文献类型：
--
作者：
Katoh M
额外性梳样（ASXL）1、ASXL 2和ASXL 3是果蝇Asx基因的人类同源物，其参与多梳组阻遏物复合物（PRC）和三胸组（trxG）激活物复合物的调节或募集。ASXL蛋白由ASXN、ASXH、ASXM 1、ASXM 2和PHD结构域组成。ASXL 1直接与BAP 1、KDM 1A（LSD 1）、NCOA 1和核激素受体（NHRs）（如视黄酸受体、雌激素受体和雄激素受体）相互作用。ASXL家族成员是表观遗传支架蛋白，其将表观遗传调节因子和转录因子组装到具有组蛋白修饰的特定基因组位点。ASXL 1通过与PRC 2的相互作用参与转录抑制，并且还通过与BAP 1和/或NHR复合物的相互作用促进转录调节。人类ASXL 1和ASXL 3的生殖系突变发生在Bohring-Opitz和相关综合征中。宫颈癌中发生ASXL 1的扩增和过表达。ASXL 1的截短突变发生在具有微卫星不稳定性（MSI）的结直肠癌、恶性骨髓性疾病、慢性淋巴细胞白血病、头颈部鳞状细胞癌以及肝癌、前列腺癌和乳腺癌中; ASXL 2的截短突变发生在前列腺癌、胰腺癌和乳腺癌中，并且在黑色素瘤中观察到ASXL 3的截短突变。EPC 1-ASXL 2基因融合发生在成人T细胞白血病/淋巴瘤中。伴有ASXL 1截短突变失调的髓系恶性肿瘤预后差。ASXL家族成员被认为是肿瘤抑制或致癌的背景依赖性的方式。
Additional sex combs-like (ASXL)1, ASXL2 and ASXL3 are human homologues of the Drosophila Asx gene that are involved in the regulation or recruitment of the Polycomb-group repressor complex (PRC) and trithorax-group (trxG) activator complex. ASXL proteins consist of ASXN, ASXH, ASXM1, ASXM2 and PHD domains. ASXL1 directly interacts with BAP1, KDM1A (LSD1), NCOA1 and nuclear hormone receptors (NHRs), such as retinoic acid receptors, oestrogen receptor and androgen receptor. ASXL family members are epigenetic scaffolding proteins that assemble epigenetic regulators and transcription factors to specific genomic loci with histone modifications. ASXL1 is involved in transcriptional repression through an interaction with PRC2 and also contributes to transcriptional regulation through interactions with BAP1 and/or NHR complexes. Germ-line mutations of human ASXL1 and ASXL3 occur in Bohring-Opitz and related syndromes. Amplification and overexpression of ASXL1 occur in cervical cancer. Truncation mutations of ASXL1 occur in colorectal cancers with microsatellite instability (MSI), malignant myeloid diseases, chronic lymphocytic leukaemia, head and neck squamous cell carcinoma, and liver, prostate and breast cancers; those of ASXL2 occur in prostate cancer, pancreatic cancer and breast cancer and those of ASXL3 are observed in melanoma. EPC1-ASXL2 gene fusion occurs in adult T-cell leukaemia/lymphoma. The prognosis of myeloid malignancies with misregulating truncation mutations of ASXL1 is poor. ASXL family members are assumed to be tumour suppressive or oncogenic in a context-dependent manner.
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影响因子：
4.5
作者：
Farber CR;Bennett BJ;Orozco L;Zou W;Lira A;Kostem E;Kang HM;Furlotte N;Berberyan A;Ghazalpour A;Suwanwela J;Drake TA;Eskin E;Wang QT;Teitelbaum SL;Lusis AJ
通讯作者：
Lusis AJ
影响因子：
28.5
作者：
Gelsi-Boyer V;Brecqueville M;Devillier R;Murati A;Mozziconacci MJ;Birnbaum D
通讯作者：
Birnbaum D
影响因子：
50.3
作者：
Abdel-Wahab O;Adli M;LaFave LM;Gao J;Hricik T;Shih AH;Pandey S;Patel JP;Chung YR;Koche R;Perna F;Zhao X;Taylor JE;Park CY;Carroll M;Melnick A;Nimer SD;Jaffe JD;Aifantis I;Bernstein BE;Levine RL
通讯作者：
Levine RL
影响因子：
20.3
作者：
Fisher, Cynthia L.;Pineault, Nicolas;Brock, Hugh W.
通讯作者：
Brock, Hugh W.
影响因子：
64.8
作者：
Berger, Michael F.;Hodis, Eran;Heffernan, Timothy P.;Deribe, Yonathan Lissanu;Lawrence, Michael S.;Protopopov, Alexei;Ivanova, Elena;Watson, Ian R.;Nickerson, Elizabeth;Ghosh, Papia;Zhang, Hailei;Zeid, Rhamy;Ren, Xiaojia;Cibulskis, Kristian;Sivachenko, Andrey Y.;Wagle, Nikhil;Sucker, Antje;Sougnez, Carrie;Onofrio, Robert;Ambrogio, Lauren;Auclair, Daniel;Fennell, Timothy;Carter, Scott L.;Drier, Yotam;Stojanov, Petar;Singer, Meredith A.;Voet, Douglas;Jing, Rui;Saksena, Gordon;Barretina, Jordi;Ramos, Alex H.;Pugh, Trevor J.;Stransky, Nicolas;Parkin, Melissa;Winckler, Wendy;Mahan, Scott;Ardlie, Kristin;Baldwin, Jennifer;Wargo, Jennifer;Schadendorf, Dirk;Meyerson, Matthew;Gabriel, Stacey B.;Golub, Todd R.;Wagner, Stephan N.;Lander, Eric S.;Getz, Gad;Chin, Lynda;Garraway, Levi A.
通讯作者：
Garraway, Levi A.