Calcineurin Regulates Cyclin D1 Accumulation in Growth-stimulated Fibroblasts
AUTOR(ES)
Kahl, Christina R.
FONTE
The American Society for Cell Biology
RESUMO
Calcium (Ca2+) and calmodulin (CaM) are required for progression of mammalian cells from quiescence into S phase. In multiple cell types, cyclosporin A causes a G1 cell cycle arrest, implicating the serine/threonine phosphatase calcineurin as one Ca2+/CaM-dependent enzyme required for G1 transit. Here, we show, in diploid human fibroblasts, that cyclosporin A arrested cells in G1 before cyclin D/cdk4 complex activation and retinoblastoma hyperphosphorylation. This arrest occurred in early G1 with low levels of cyclin D1 protein. Because cyclin D1 mRNA was induced normally in the cyclosporin A-treated cells, we analyzed the half-life of cyclin D1 in the presence of cyclosporin A and found no difference from control cells. However, cyclosporin A treatment dramatically reduced cyclin D1 protein synthesis. Although these pharmacological experiments suggested that calcineurin regulates cyclin D1 synthesis, we evaluated the effects of overexpression of activated calcineurin on cyclin D1 synthesis. In contrast to the reduction of cyclin D1 with cyclosporin A, ectopic expression of calcium/calmodulin-independent calcineurin promoted synthesis of cyclin D1 during G1 progression. Therefore, calcineurin is a Ca2+/CaM-dependent target that regulates cyclin D1 accumulation in G1.
ACESSO AO ARTIGO
http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=379279Documentos Relacionados
- Regulation of Ribosomal Protein mRNA Content and Translation in Growth-Stimulated Mouse Fibroblasts
- Hsc70 Regulates Accumulation of Cyclin D1 and Cyclin D1-Dependent Protein Kinase
- fos/jun repression of cardiac-specific transcription in quiescent and growth-stimulated myocytes is targeted at a tissue-specific cis element.
- Cyclin D1 Expression Mediated by Phosphatidylinositol 3-Kinase through mTOR-p70S6K-Independent Signaling in Growth Factor-Stimulated NIH 3T3 Fibroblasts
- The 5'-flanking region of the mouse thymidylate synthase gene is necessary but not sufficient for normal regulation in growth-stimulated cells.
