Steroid receptor coactivators – their role in immunity

Abstract

Steroid Receptor Coactivators (SRCs) are essential regulators of transcription with a wide range of impact on human physiology and pathology. In immunology, SRCs play multiple roles; they are involved in the regulation of nuclear factor-κB (NF-κB), macrophage (MΦ) activity, lymphoid cells proliferation, development and function, to name just a few. The three SRC family members, SRC-1, SRC-2 and SRC-3, can exert their immunological function either in an independent manner or act in synergy with each other. In certain biological contexts, one SRC family member can compensate for lack of activity of another member, while in other cases one SRC can exert a biological function that competes against the function of another family counterpart. In this review we illustrate the diverse biological functionality of the SRCs with regard to their role in immunity. In the light of recent development of SRC small molecule inhibitors and stimulators, we discuss their potential relevance as modulators of the immunological activity of the SRCs for therapeutic purposes.

Steroid receptor coactivators in Treg and Th17 cell biology and function

“…Since the discovery and cloning of the first SRC, SRC-1, almost 30 years ago ( 6 ), these coactivators have been established as critical regulators of gene expression with broad range of impact on human physiology and pathology. Specifically in immunology, the SRCs have diverse biological functionalities that include interactions with major immune system TFs such as NF-κB and RORγt, involvement in immune cell fate determination and development as well as control of their proliferation ( 11 ). In this review, we have highlighted the roles of the SRCs in the biology of two, functionally antagonistic, subtypes of CD4 + T cells – Tregs and Th17 cells; SRC-3 is one of the most highly expressed coactivators in Tregs and is important for their suppressive function.…”

“…All three SRCs play important roles in major physiological and pathological processes such as fertility, metabolism, wound healing, development, immunology and oncogenesis ( 8 – 10 ). The importance of the SRCs in immunology is understudied but is evidenced by studies that show their participation in fate determination and function of lymphocytes and macrophages, regulation of lymphoproliferation and the ability to interact with and coordinate the transcriptional activity of DNA-binding transcription factors (TFs) such as NF-κB ( 11 ).…”

Small molecule inhibitors of RORγt for Th17 regulation in inflammatory and autoimmune diseases

“…Runx1 increases RORγt expression via TGF-β signaling pathway [ 102 ]. SRCs including the SRC1 (NCoA1), SRC2 (NCoA2), and SRC3 (NCoA3), participate in most NRs transcription activity [ 103 ]. RORγt recruits SRCs to regulate thymus cell survival in vivo [ 83 ].…”

AIB1/SRC-3/NCOA3 function in estrogen receptor alpha positive breast cancer

“…AIB1 also supports the maintenance of embryonic stem cell pluripotency through regulation of essential pluripotency genes such as Klf4, Tbx3 and Dax-1 ( 76 ). Additionally, AIB1 plays a role in immunity which is in part due to its interaction with the inflammatory regulator NF-κB (reviewed in 77 ). A recent study by Han et al.…”