In:
Molecular Biology of the Cell, American Society for Cell Biology (ASCB), Vol. 15, No. 4 ( 2004-04), p. 1833-1842
Abstract:
Calcium (Ca 2+ ) and calmodulin (CaM) are required for progression of mammalian cells from quiescence into S phase. In multiple cell types, cyclosporin A causes a G 1 cell cycle arrest, implicating the serine/threonine phosphatase calcineurin as one Ca 2+ /CaM-dependent enzyme required for G 1 transit. Here, we show, in diploid human fibroblasts, that cyclosporin A arrested cells in G 1 before cyclin D/cdk4 complex activation and retinoblastoma hyperphosphorylation. This arrest occurred in early G 1 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 G 1 progression. Therefore, calcineurin is a Ca 2+ /CaM-dependent target that regulates cyclin D1 accumulation in G 1 .
Type of Medium:
Online Resource
ISSN:
1059-1524
,
1939-4586
DOI:
10.1091/mbc.e03-10-0730
Language:
English
Publisher:
American Society for Cell Biology (ASCB)
Publication Date:
2004
detail.hit.zdb_id:
1474922-1
SSG:
12
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