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Publication : A novel function for Cyclin A2: control of cell invasion via RhoA signaling.

First Author  Arsic N Year  2012
Journal  J Cell Biol Volume  196
Issue  1 Pages  147-62
PubMed ID  22232705 Mgi Jnum  J:180654
Mgi Id  MGI:5306814 Doi  10.1083/jcb.201102085
Citation  Arsic N, et al. (2012) A novel function for Cyclin A2: control of cell invasion via RhoA signaling. J Cell Biol 196(1):147-62
abstractText  Cyclin A2 plays a key role in cell cycle regulation. It is essential in embryonic cells and in the hematopoietic lineage yet dispensable in fibroblasts. In this paper, we demonstrate that Cyclin A2-depleted cells display a cortical distribution of actin filaments and increased migration. These defects are rescued by restoration of wild-type Cyclin A2, which directly interacts with RhoA, or by a Cyclin A2 mutant unable to associate with Cdk. In vitro, Cyclin A2 potentiates the exchange activity of a RhoA-specific guanine nucleotide exchange factor. Consistent with this, Cyclin A2 depletion enhances migration of fibroblasts and invasiveness of transformed cells via down-regulation of RhoA activity. Moreover, Cyclin A2 expression is lower in metastases relative to primary colon adenocarcinoma in matched human tumors. All together, these data show that Cyclin A2 negatively controls cell motility by promoting RhoA activation, thus demonstrating a novel Cyclin A2 function in cytoskeletal rearrangements and cell migration.
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