TY - JOUR
T1 - Regulation of SMRT corepressor dimerization and composition by MAP kinase phosphorylation
AU - Varlakhanova, Natalia
AU - Hahm, Johnnie B.
AU - Privalsky, Martin L.
PY - 2011/1/30
Y1 - 2011/1/30
N2 - The SMRT (Silencing Mediator of Retinoid and Thyroid hormone receptors) corepressor mediates gene repression by nuclear receptors and other transcriptional factors. The SMRT protein serves as a key nucleating core that organizes the assembly of a larger corepressor complex. We report here that SMRT interacts with itself to form a protein dimer, and that Erk2, a mitogen-activated protein (MAP) kinase, disrupts this SMRT self-dimerization in vitro and in vivo. Notably Erk2 phosphorylation also results in a re-organization of the overall corepressor complex, characterized by a reduced sedimentation coefficient, partial release of HDAC3, TBL-1, and TBLR-1, and inhibition of transcriptional repression. We propose that SMRT dimers form the central platform on which additional corepressor components assemble, and that kinase signaling modifies the architecture, composition, and function of this complex. These observations contribute to our understanding of how the SMRT corepressor complex assembles and is regulated during cell proliferation and differentiation.
AB - The SMRT (Silencing Mediator of Retinoid and Thyroid hormone receptors) corepressor mediates gene repression by nuclear receptors and other transcriptional factors. The SMRT protein serves as a key nucleating core that organizes the assembly of a larger corepressor complex. We report here that SMRT interacts with itself to form a protein dimer, and that Erk2, a mitogen-activated protein (MAP) kinase, disrupts this SMRT self-dimerization in vitro and in vivo. Notably Erk2 phosphorylation also results in a re-organization of the overall corepressor complex, characterized by a reduced sedimentation coefficient, partial release of HDAC3, TBL-1, and TBLR-1, and inhibition of transcriptional repression. We propose that SMRT dimers form the central platform on which additional corepressor components assemble, and that kinase signaling modifies the architecture, composition, and function of this complex. These observations contribute to our understanding of how the SMRT corepressor complex assembles and is regulated during cell proliferation and differentiation.
KW - Corepressor complex
KW - Dimer
KW - Erk
KW - MAP kinases
KW - SMRT
UR - http://www.scopus.com/inward/record.url?scp=78650521041&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=78650521041&partnerID=8YFLogxK
U2 - 10.1016/j.mce.2010.10.010
DO - 10.1016/j.mce.2010.10.010
M3 - Article
C2 - 20965228
AN - SCOPUS:78650521041
VL - 332
SP - 180
EP - 188
JO - Molecular and Cellular Endocrinology
JF - Molecular and Cellular Endocrinology
SN - 0303-7207
IS - 1-2
ER -