Molecular structure and biological function of the cancer-amplified nuclear receptor coactivator SRC-3/AIB1.
Nuclear hormone receptors are ligand-dependent transcription factors that require coactivators to regulate target gene expression. The steroid receptor coactivator-3 (SRC-3), also known as p/CIP, RAC3, AIB1, ACTR and TRAM-1, is a cancer-amplified coactivator in the SRC gene family that also contains SRC-1 and TIF2/GRIP1. SRC-3 interacts with nuclear receptors and certain other transcription factors, recruits histone acetyltransferases and methyltransferases for chromatin remodeling and facilitates target gene transcription. Accumulated results from both ex vivo and animal model studies indicate that SRC-3 plays important roles in many biological processes involving cell proliferation, cell migration, cell differentiation, somatic growth, sexual maturation, female reproductive function, vasoprotection and breast cancer. This article summarizes our current knowledge about SRC-3 under the following topics: molecular cloning and characterization; molecular structure and functional mechanisms; SRC-3 as a molecular target of growth factors and cytokines; organization and expression of the SRC-3 gene; generation and characterization of SRC-3 knockout mice; role of SRC-3 in the vasoprotective effects of estrogen; role of SRC-3 in cell migration, proliferation and cancers.
Liao
Lan
L
Department of Molecular and Cellular Biology, Baylor College of Medicine, One Baylor Plaza, Houston, TX 77030, USA.
Kuang
Shao-Qing
SQ
Yuan
Yuhui
Y
Gonzalez
Sonia M
SM
O'Malley
Bert W
BW
Xu
Jianming
J
D000123:Acetyltransferases; D000818:Animals; D001943:Breast Neoplasms / Q000378:metabolism / Q000473:pathology; D002454:Cell Differentiation; D002455:Cell Division; D002465:Cell Movement; D002843:Chromatin / Q000378:metabolism; D003001:Cloning, Molecular; D005091:Exons; D005260:Female; D051548:Histone Acetyltransferases; D006801:Humans; D007438:Introns; D008024:Ligands; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D008954:Models, Biological; D008957:Models, Genetic; D009369:Neoplasms / Q000378:metabolism; D056921:Nuclear Receptor Coactivator 3; D015513:Oncogene Proteins; D011471:Prostatic Neoplasms / Q000473:pathology; D017434:Protein Structure, Tertiary; D013329:Structure-Activity Relationship; D015534:Trans-Activators / Q000737:chemistry* / Q000235:genetics*; D014158:Transcription, Genetic
D002843:Chromatin; D008024:Ligands; D015513:Oncogene Proteins; D015534:Trans-Activators; D000123:Acetyltransferases; D051548:Histone Acetyltransferases; C538866:NCOA3 protein, human; C538867:Ncoa3 protein, mouse; D056921:Nuclear Receptor Coactivator 3