RhoE Inhibits Cell Cycle Progression and Ras-Induced Transformation
| Autor: | Rosa M. Guasch, Priam Villalonga, Anne J. Ridley, Kirsi Riento |
|---|---|
| Rok vydání: | 2004 |
| Předmět: |
Cyclin-Dependent Kinase Inhibitor p21
rho GTP-Binding Proteins RHOA Cyclin E Cell cycle checkpoint Cell Cycle Proteins Biology Transfection Retinoblastoma Protein Mice Cyclins Animals Cyclin D1 Cell Growth and Development Molecular Biology Cytoskeleton Cyclin Cell growth Rnd3 Cell Cycle GTPase-Activating Proteins Retinoblastoma protein Cell Biology Cell cycle Actins Recombinant Proteins E2F Transcription Factors Cell biology DNA-Binding Proteins Proto-Oncogene Proteins c-raf Cell Transformation Neoplastic Gene Expression Regulation NIH 3T3 Cells ras Proteins biology.protein Cancer research Cisplatin Signal Transduction Transcription Factors |
| Zdroj: | Molecular and Cellular Biology. 24:7829-7840 |
| ISSN: | 1098-5549 |
| DOI: | 10.1128/mcb.24.18.7829-7840.2004 |
| Popis: | Rho GTPases are major regulators of cytoskeletal dynamics, but they also affect cell proliferation, transformation, and oncogenesis. RhoE, a member of the Rnd subfamily that does not detectably hydrolyze GTP, inhibits RhoA/ROCK signaling to promote actin stress fiber and focal adhesion disassembly. We have generated fibroblasts with inducible RhoE expression to investigate the role of RhoE in cell proliferation. RhoE expression induced a loss of stress fibers and cell rounding, but these effects were only transient. RhoE induction inhibited cell proliferation and serum-induced S-phase entry. Neither ROCK nor RhoA inhibition accounted for this response. Consistent with its inhibitory effect on cell cycle progression, RhoE expression was induced by cisplatin, a DNA damage-inducing agent. RhoE-expressing cells failed to accumulate cyclin D1 or p21(cip1) protein or to activate E2F-regulated genes in response to serum, although ERK, PI3-K/Akt, FAK, Rac, and cyclin D1 transcription was activated normally. The expression of proteins that bypass the retinoblastoma (pRb) family cell cycle checkpoint, including human papillomavirus E7, adenovirus E1A, and cyclin E, rescued cell cycle progression in RhoE-expressing cells. RhoE also inhibited Ras- and Raf-induced fibroblast transformation. These results indicate that RhoE inhibits cell cycle progression upstream of the pRb checkpoint. |
| Databáze: | OpenAIRE |
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