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PMID: 9501191 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, Non-P.H.S. Research Support, U.S. Gov't, P.H.S.

Diverse signaling pathways modulate nuclear receptor recruitment of N-CoR and SMRT complexes.

Proceedings of the National Academy of Sciences of the United States of America ·Vol. 95 ·No. 6 ·1998-03-17 ·Pages 2920-5

Lavinsky RM, Jepsen K, Heinzel T, Torchia J, Mullen TM, Schiff R, Del-Rio AL, Ricote M, Ngo S, Gemsch J, Hilsenbeck SG, Osborne CK, Glass CK, Rosenfeld MG, Rose DW

Abstract

Several lines of evidence indicate that the nuclear receptor corepressor (N-CoR) complex imposes ligand dependence on transcriptional activation by the retinoic acid receptor and mediates the inhibitory effects of estrogen receptor antagonists, such as tamoxifen, suppressing a constitutive N-terminal, Creb-binding protein/coactivator complex-dependent activation domain. Functional interactions between specific receptors and N-CoR or SMRT corepressor complexes are regulated, positively or negatively, by diverse signal transduction pathways. Decreased levels of N-CoR correlate with the acquisition of tamoxifen resistance in a mouse model system for human breast cancer. Our data suggest that N-CoR- and SMRT-containing complexes act as rate-limiting components in the actions of specific nuclear receptors, and that their actions are regulated by multiple signal transduction pathways.

MeSH Terms
Animals Breast Neoplasms/metabolism DNA-Binding Proteins/metabolism Disease Models, Animal Drug Resistance Estrogen Antagonists/pharmacology Gene Expression Regulation Genes, Reporter Humans Mice Models, Biological Nuclear Proteins/metabolism Nuclear Receptor Co-Repressor 1 Nuclear Receptor Co-Repressor 2 Protein Binding Protein Kinases/metabolism Receptors, Estrogen/metabolism Receptors, Retinoic Acid/metabolism Repressor Proteins/metabolism Signal Transduction Tamoxifen/pharmacology
Chemicals
DNA-Binding Proteins Estrogen Antagonists NCOR1 protein, human NCOR2 protein, human Ncor1 protein, mouse Ncor2 protein, mouse Nuclear Proteins Nuclear Receptor Co-Repressor 1 Nuclear Receptor Co-Repressor 2 Receptors, Estrogen Receptors, Retinoic Acid Repressor Proteins Tamoxifen Protein Kinases
Authors & Affiliations
15 authors, click to expand affiliations / ORCID
Lavinsky R M
Howard Hughes Medical Institute, Department and School of Medicine, University of California at San Diego, La Jolla, CA 92093-0648, USA.
Jepsen K
Heinzel T
Torchia J
Mullen T M
Schiff R
Del-Rio A L
Ricote M
Ngo S
Gemsch J
Hilsenbeck S G
Osborne C K
Glass C K
Rosenfeld M G
Rose D W
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Article Info
Journal
Proceedings of the National Academy of Sciences of the United States of America
Abbr.
Proc Natl Acad Sci U S A
ISSN
0027-8424
DOI
10.1073/pnas.95.6.2920
Published
1998-03-17
Pages
2920-5
Language
English
Region
United States
NLM ID
7505876
PMCID
PMC19670
Subset
IM
Grants
NCI NIH HHS · P30 CA054174 · United States
NCI NIH HHS · P50 CA058183 · United States
NCI NIH HHS · P30CA54174 · United States
NCI NIH HHS · P50CA58183 · United States
External Links
PubMed source DOI: 10.1073/pnas.95.6.2920 PMC Full Text View journal details
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