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Cdk1/cyclin B‐mediated phosphorylation regulates SREBP1
Author(s) -
BengoecheaAlonso Maria Teresa,
Ericsson Johan
Publication year - 2007
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.21.5.a290-a
Subject(s) - sterol regulatory element binding protein , cyclin dependent kinase 1 , phosphorylation , microbiology and biotechnology , mitosis , cyclin b1 , cell growth , serine , biology , phosphoserine , biochemistry , chemistry , cell cycle , transcription factor , cell , gene
The sterol regulatory element‐binding protein (SREBP) family of transcription factors controls the biosynthesis of cholesterol and other lipids, and lipid synthesis is critical for cell growth and proliferation. We have found that the mature forms of SREBP1a and SREBP1c are hyperphosphorylated in mitotic cells, giving rise to a phosphoepitope recognized by the mitotic protein monoclonal‐2 (MPM‐2) antibody. In addition, we have found that mature SREBP1 is stabilized in a phosphorylation‐dependent manner during mitosis. The major MPM‐2 epitope is a serine residue in the C terminus of mature SREBP1. Using phosphorylation‐specific antibodies, we demonstrate that endogenous SREBP1 is phosphorylated on this residue during mitosis. Mature SREBP1 interacts with Cdk1/cyclin B in mitotic cells and we demonstrate that Cdk1 phosphorylates SREBP1, both in vitro and in vivo. Mutation of the phosphorylated serine residue regulates both the expression and activity of SREBP1. Thus, our results demonstrate that the activity of mature SREBP1 is regulated by the phosphorylation of a specific amino acid residue during the cell cycle, suggesting that SREBP1 may provide a link between lipid synthesis, proliferation and cell growth. This hypothesis was supported by our observation that siRNA‐mediated inactivation of SREBP1 attenuated cell growth.