Chen J D, Umesono K, Evans R M
The Salk Institute for Biological Studies, Howard Hughes Medical Institute, La Jolla, CA 92037, USA.
Proc Natl Acad Sci U S A. 1996 Jul 23;93(15):7567-71. doi: 10.1073/pnas.93.15.7567.
Transcriptional repression represents an important component in the regulation of cell differentiation and oncogenesis mediated by nuclear hormone receptors. Hormones act to relieve repression, thus allowing receptors to function as transcriptional activators. The transcriptional corepressor SMRT was identified as a silencing mediator for retinoid and thyroid hormone receptors. SMRT is highly related to another corepressor, N-CoR, suggesting the existence of a new family of receptor-interacting proteins. We demonstrate that SMRT is a ubiquitous nuclear protein that interacts with unliganded receptor heterodimers in mammalian cells. Furthermore, expression of the receptor-interacting domain of SMRT acts as an antirepressor, suggesting the potential importance of splicing variants as modulators of thyroid hormone and retinoic acid signaling.
转录抑制是核激素受体介导的细胞分化和肿瘤发生调控中的一个重要组成部分。激素发挥作用以解除抑制，从而使受体能够作为转录激活因子发挥功能。转录共抑制因子SMRT被鉴定为类视黄醇和甲状腺激素受体的沉默介质。SMRT与另一种共抑制因子N-CoR高度相关，提示存在一个新的受体相互作用蛋白家族。我们证明SMRT是一种普遍存在的核蛋白，在哺乳动物细胞中与未结合配体的受体异二聚体相互作用。此外，SMRT的受体相互作用结构域的表达起到抗抑制作用，提示剪接变体作为甲状腺激素和视黄酸信号调节剂的潜在重要性。
