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Cell cycle: Checkpoint Maintenance

STKE  12 Oct 1999:
Vol. 1999, Issue 3, pp. tw4
DOI: 10.1126/stke.1999.3.tw4

The once inexplicable actions of 14-3-3 proteins gradually become clearer. Members of this protein family bind to phosphorylated proteins and appear to prevent their movement to the nucleus. Chan et al. made human colorectal cancer cells that lacked expression of a particular 14-3-3 protein, 14-3-3sigma. These cells could initiate arrest of the cell cycle in G2 phase in response to DNA damage, but did not maintain that arrest as they normally would if the 14-3-3sigma protein was present. The mutant cells failed to retain cyclin B1 and the cyclin-dependent kinase Cdc2 in the cytoplasm. Movement of cyclin B1--Cdc2 complexes to the nucleus promoted mitosis and caused cell death or "mitotic catastrophe". The emerging picture is that initiation of G2 arrest in response to DNA damage involves interaction of other 14-3-3 family members with the phosphatase Cdc25, whereas maintenance of such arrest requires 14-3-3sigma, which sustains arrest by holding cyclin B1 and Cdc2 outside of the nucleus.

Chan, T. A., Hermeking, H., Lengauer, C., Kinzler, K. W., and Vogelstein, B. (1999) 14-3-3sigma is required to prevent mitotic catastrophe after DNA damage. Nature 401: 616-620. [Online Journal]