Identification and Characterization of SAP25, a Novel Component of the mSin3 Corepressor Complex
- Shiio, Yuzuru Children's Cancer Research Institute, The University of Texas Health Science Center, San Antonio, Texas 78229-3900
- Rose, David W. Department of Medicine and Cancer Center, University of California at San Diego, San Diego, California 92093-0673
- Aur, Radin Department of Medicine and Cancer Center, University of California at San Diego, San Diego, California 92093-0673
- Donohoe, Sam Institute for Systems Biology, Seattle, Washington 98103-8904
- Aebersold, Ruedi Institute for Molecular Systems Biology, ETH-Zurich, and Faculty of Natural Sciences, University of Zurich, Zurich, Switzerland
- Eisenman, Robert N. Division of Basic Sciences, Fred Hutchinson Cancer Research Center, Seattle, Washington 98109-1024
Published in:
- Molecular and Cellular Biology. - American Society for Microbiology. - 2006, vol. 26, no. 4, p. 1386-1397
English
ABSTRACT
The
transcriptional corepressor mSin3 is associated with histone
deacetylases (HDACs) and is utilized by many DNA-binding
transcriptional repressors. We have cloned and characterized a novel
mSin3A-binding protein, SAP25. SAP25 binds to the PAH1 domain of
mSin3A, associates with the mSin3A-HDAC complex in vivo, and represses
transcription when tethered to DNA. SAP25 is required for
mSin3A-mediated, but not N-CoR-mediated, repression. SAP25 is a
nucleocytoplasmic shuttling protein, actively exported from the nucleus
by a CRM1-dependent mechanism. A fraction of SAP25 is located in
promyelocytic leukemia protein (PML) nuclear bodies, and
PML induces a striking nuclear accumulation of SAP25. An isotope-coded
affinity tag quantitative proteomic analysis of the SAP25 complex
revealed that SAP25 is associated with several components of the mSin3
complex, nuclear export machinery, and regulators of transcription and
cell cycle. These results suggest that SAP25 is a novel core component
of the mSin3 corepressor complex whose subcellular location is
regulated by
PML.
transcriptional corepressor mSin3 is associated with histone
deacetylases (HDACs) and is utilized by many DNA-binding
transcriptional repressors. We have cloned and characterized a novel
mSin3A-binding protein, SAP25. SAP25 binds to the PAH1 domain of
mSin3A, associates with the mSin3A-HDAC complex in vivo, and represses
transcription when tethered to DNA. SAP25 is required for
mSin3A-mediated, but not N-CoR-mediated, repression. SAP25 is a
nucleocytoplasmic shuttling protein, actively exported from the nucleus
by a CRM1-dependent mechanism. A fraction of SAP25 is located in
promyelocytic leukemia protein (PML) nuclear bodies, and
PML induces a striking nuclear accumulation of SAP25. An isotope-coded
affinity tag quantitative proteomic analysis of the SAP25 complex
revealed that SAP25 is associated with several components of the mSin3
complex, nuclear export machinery, and regulators of transcription and
cell cycle. These results suggest that SAP25 is a novel core component
of the mSin3 corepressor complex whose subcellular location is
regulated by
PML.
- Language
-
- English
- Open access status
- bronze
- Identifiers
-
- DOI 10.1128/mcb.26.4.1386-1397.2006
- ISSN 0270-7306
- Persistent URL
- https://sonar.rero.ch/global/documents/110691
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