Author:
Nikolai Bryan C.,Jain Prashi,Cardenas David L.,York Brian,Feng Qin,McKenna Neil J.,Dasgupta Subhamoy,Lonard David M.,O’Malley Bert W.
Abstract
AbstractA subset of CD4 + lymphocytes, regulatory T cells (Tregs), are necessary for central tolerance and function as suppressors of autoimmunity against self-antigens. The SRC-3 coactivator is an oncogene in multiple cancers and is capable of potentiating numerous transcription factors in a wide variety of cell types. Src-3 knockout mice display broad lymphoproliferation and hypersensitivity to systemic inflammation. Using publicly available bioinformatics data and directed cellular approaches, we show that SRC-3 also is highly enriched in Tregs in mice and humans. Human Tregs lose phenotypic characteristics when SRC-3 is depleted or pharmacologically inhibited, including failure of induction from resting T cells and loss of the ability to suppress proliferation of stimulated T cells. These data support a model for SRC-3 as a coactivator that actively participates in protection from autoimmunity and may support immune evasion of cancers by contributing to the biology of Tregs.
Funder
Cancer Prevention and Research Institute of Texas
National Institutes of Health
Publisher
Springer Science and Business Media LLC
Reference25 articles.
1. Anzick, S. L. AIB1, a steroid receptor coactivator amplified in breast and ovarian cancer. Science 277, 965–968 (1997).
2. Guan, X. Y. et al. Hybrid selection of transcribed sequences from microdissected DNA: isolation of genes within amplified region at 20q11-q13.2 in breast cancer. Cancer Res. 56, 3446–3450 (1996).
3. Burandt, E. et al. Prognostic relevance of AIB1 (NCoA3) amplification and overexpression in breast cancer. Breast Cancer Res. Treat. 137, 745–753 (2013).
4. Dasgupta, S., Lonard, D. M. & O’Malley, B. W. Nuclear receptor coactivators: master regulators of human health and disease. Annu. Rev. Med. 65, 279–292 (2014).
5. Wu, R.-C. et al. Selective phosphorylations of the SRC-3/AIB1 coactivator integrate genomic reponses to multiple cellular signaling pathways. Mol. Cell 15, 937–949 (2004).
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