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PMID: 15456879 Published · ppublish English Journal Article

Bromodomain protein Brd4 binds to GTPase-activating SPA-1, modulating its activity and subcellular localization.

Molecular and cellular biology ·Vol. 24 ·No. 20 ·2004-10-00 ·Pages 9059-69

Farina A, Hattori M, Qin J, Nakatani Y, Minato N, Ozato K

Abstract

Brd4 is a mammalian protein that contains a double bromodomain. It binds to chromatin and regulates cell cycle progression at multiple stages. By immunopurification and mass spectrometry, we identified a Rap GTPase-activating protein (GAP), signal-induced proliferation-associated protein 1 (SPA-1), as a factor that interacts with Brd4. SPA-1 localizes to the cytoplasm and to a lesser degree in the nucleus, while Brd4 resides in the nucleus. Bifluorescence complementation revealed that Brd4 and SPA-1 interact with each other in the nucleus of living cells. Supporting the functional importance of the interaction, Brd4 enhanced Rap GAP activity of SPA-1. Furthermore ectopic expression of SPA-1 and Brd4 redirected subcellular localization of the partner and disrupted normal cell cycle progression. These effects were, however, reversed by coexpression of the two proteins, indicating that a proper balance between Brd4 and SPA-1 in G2 is required for cell division. This work reveals a novel link between Brd4 and a GTPase-dependent mitogenic signaling pathway.

MeSH Terms
Animals Cell Cycle/physiology Cell Cycle Proteins Cell Nucleus/metabolism GTPase-Activating Proteins/genetics,metabolism HeLa Cells Humans Mice NIH 3T3 Cells Nuclear Proteins/genetics,metabolism Oncogene Proteins, Fusion/genetics,metabolism Protein Binding Signal Transduction/physiology Subcellular Fractions/metabolism Transcription Factors rap GTP-Binding Proteins/metabolism rap1 GTP-Binding Proteins/metabolism
Chemicals
BRD4 protein, human Cell Cycle Proteins GTPase-Activating Proteins Nuclear Proteins Oncogene Proteins, Fusion SIPA1 protein, human Transcription Factors RAP2A protein, human rap GTP-Binding Proteins rap1 GTP-Binding Proteins
Authors & Affiliations
6 authors, click to expand affiliations / ORCID
Farina Andrea
Laboratory of Molecular Growth Regulation, National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD 20892-2753, USA.
Hattori Masakazu
Qin Jun
Nakatani Yoshihiro
Minato Nagahiro
Ozato Keiko
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Article Info
Journal
Molecular and cellular biology
Abbr.
Mol Cell Biol
ISSN
0270-7306
DOI
10.1128/MCB.24.20.9059-9069.2004
Published
2004-10-00
Pages
9059-69
Language
English
Region
United States
NLM ID
8109087
PMCID
PMC517877
Subset
IM
External Links
PubMed source DOI: 10.1128/MCB.24.20.9059-9069.2004 PMC Full Text View journal details
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