Functional proteomics of the epigenetic regulators ASXL1, ASXL2 and ASXL3: a convergence of proteomics and epigenetics for translational medicine.
Expert Rev Proteomics
; 12(3): 317-28, 2015 Jun.
Article
em En
| MEDLINE
| ID: mdl-25835095
ABSTRACT
ASXL1, ASXL2 and ASXL3 are epigenetic scaffolds for BAP1, EZH2, NCOA1, nuclear receptors and WTIP. Here, functional proteomics of the ASXL family members are reviewed with emphasis on mutation spectra, the ASXM2 domain and the plant homeodomain (PHD) finger. Copy number gains of ASXL1 occur in chromosome 20q11.2 duplication syndrome and cervical cancer. Truncation mutations of ASXLs occur in autism, Bohring-Opitz and related syndromes, hematological malignancies and solid tumors, such as prostate cancer, breast cancer and high-grade glioma, which are gain- or loss-of-function mutations. The ASXM2 domain is a binding module for androgen receptor and estrogen receptor α, while the PHD finger is a ligand of WTIP LIM domains and a putative chromatin-binding module. Phylogenetic analyses of 139 human PHD fingers revealed that ASXL PHD fingers cluster with those of BPTF, DIDO, ING1, KDM5A (JARID1A), KMT2E (MLL5), PHF2, PHF8 and PHF23. The cell context-dependent epigenetic code of ASXLs should be deciphered to develop therapeutics for human diseases.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Proteínas Repressoras
/
Fatores de Transcrição
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Proteômica
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Epigênese Genética
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Pesquisa Translacional Biomédica
Limite:
Animals
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Humans
Idioma:
En
Revista:
Expert Rev Proteomics
Assunto da revista:
BIOQUIMICA
Ano de publicação:
2015
Tipo de documento:
Article
País de afiliação:
Japão