| Autor: |
Pangon, Laurent, Sigglekow, Nicholas D., Larance, Mark, Al-Sohaily, Sam, Mladenova, Dessislava N., Selinger, Christina I., Musgrove, Elizabeth A., Kohonen-Corish, Maija R. J. |
| Zdroj: |
Genes & Cancer; September 2010, Vol. 1 Issue: 9 p917-926, 10p |
| Abstrakt: |
MCC is a potential tumor suppressor gene, which is silenced by promoter hypermethylation in a subset of colorectal cancers. However, its functions have remained poorly understood. In the present study, we describe a novel function of MCC in the DNA damage response. Several novel phosphorylation sites were identified by mass spectrometry, including 2 highly conserved ATM/ATR consensus sites at serine 118 and serine 120. In addition, exposure to ultraviolet radiation (UV), but not phleomycin, caused PI3K-dependent phosphorylation of MCC and its nuclear localization. Re-expression of MCC in HCT15 colorectal cancer cells led to a G2/M arrest, and MCC knockdown impaired the induction of a G2/M arrest following UV radiation. Finally, mutation of S118/120 to alanine did not affect MCC nuclear shuttling following UV but did impair MCC G2/M checkpoint activity. Thus, these results suggest that MCC is a novel target of the DNA damage checkpoint and that MCC is required for the complete cell cycle arrest in the G2/M phase in response to UV. |
| Databáze: |
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