期刊
EMBO JOURNAL
卷 19, 期 18, 页码 4955-4966出版社
OXFORD UNIV PRESS
DOI: 10.1093/emboj/19.18.4955
关键词
cell cycle; PI3-kinase; serum response element; transcription
资金
- NHLBI NIH HHS [P01 HL044948, HL 44948] Funding Source: Medline
- NINDS NIH HHS [NS 20498, R01 NS020498] Funding Source: Medline
- NINR NIH HHS [NRSA T32] Funding Source: Medline
Recent evidence indicates that phosphatidylinositol 3-kinase (PI3K) is a central regulator of mitosis, apoptosis and oncogenesis, Nevertheless, the mechanisms by which PI3K regulates proliferation are not well characterized. Mitogens stimulate entry into the cell cycle by inducing the expression of immediate early genes (IEGs) that in turn trigger the expression of G(1) cyclins, Here we describe a novel PI3K-regulated transcriptional cascade that is critical for mitogen regulation of the IEG, c-fos, We show that PI3K activates gene expression by transactivating SRF-dependent transcription independently of the previously described Rho and ETS TCF pathways. PI3K-stimulated cell cycle progression requires transactivation of SRF and expression of dominant-negative PI3K blocks mitogen-stimulated cell cycle progression. Furthermore, dominant-interfering SRF mutants attenuate mitogen-stimulated cell cycle progression, but are without effect on MEK-stimulated cell cycle entry. Moreover, expression of constitutively active SRP is sufficient for cell cycle entry. Thus, we delineate a novel SRF-dependent mitogenic cascade that is critical for PI3K- and growth factor-mediated cell cycle progression.
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