Nuclear receptor corepressor complexes in cancer: mechanism, function and regulation.
Nuclear receptor corepressor (NCoR) and silencing mediator for retinoid and thyroid hormone receptors (SMRT) function as corepressors for diverse transcription factors including nuclear receptors such as estrogen receptors and androgen receptors. Deregulated functions of NCoR and SMRT have been observed in many types of cancers and leukemias. NCoR and SMRT directly bind to transcription factors and nucleate the formation of stable complexes that include histone deacetylase 3, transducin b-like protein 1/TBL1-related protein 1, and G-protein pathway suppressor 2. These NCoR/SMRT-interacting proteins also show deregulated functions in cancers. In this review, we summarize the literature on the mechanism, regulation, and function of the core components of NCoR/SMRT complexes in the context of their involvement in cancers and leukemias. While the current studies support the view that the corepressors are promising targets for cancer treatment, elucidation of the mechanisms of corepressors involved in individual types of cancers is likely required for effective therapy.
Department of Pharmacological & Physiological Science, Saint Louis University School of Medicine St. Louis, Missouri 63104.
Madeline M
MM
Wong
Department of Pharmacological & Physiological Science, Saint Louis University School of Medicine St. Louis, Missouri 63104.
Chun
C
Guo
Department of Pharmacological & Physiological Science, Saint Louis University School of Medicine St. Louis, Missouri 63104.
Jinsong
J
Zhang
GPS2; HDAC3; NCoR; SMRT; TBL1; TBLR1; cancer; corepressor; transcriptional repression