MUC1-C Oncoprotein Interacts Directly With ATM And Promotes The DNA Damage Response To Ionizing Radiation  

Oleh:

Huang, Lei ; Liao, Xiaodong ; Beckett, Michael ; Li, Yuan ; Khanna, Kum Kum ; Wang, Zhugang ; Kharbanda, Surender ; Weichselbaum, Ralph ; Kufe, Donald

Jenis: Article from Article
Dalam koleksi: Genes and Cancer vol. 1 no. 3 (May 2010), page 239-250.
Topik: MUC1; ATM; DNA Damage; H2AX; Ionizing Radiation
Fulltext: 239.full.pdf (632.57KB)

Isi artikel

The ataxia-telangiectasia mutated (ATM) kinase is activated in the cellular response to ionizing radiation (IR) and is of importance to the repair of DNA double-strand breaks (DSBs). The MUC1 oncoprotein is aberrantly overexpressed in human breast carcinomas. The present work demonstrates that the MUC1 C-terminal subunit (MUC1-C) constitutively interacts with ATM in human breast cancer cells. The authors show that the MUC1-C cytoplasmic domain binds directly to ATM HEAT repeats. The results also demonstrate that the MUC1-C cytoplasmic domain binds to the ATM substrate H2AX. The functional significance of these interactions is supported by the finding that MUC1-C promotes removal of IR-induced nuclear ?H2AX foci. MUC1-C also protects against IR-induced chromosomal aberrations. In concert with these results, MUC1-C blocks IR-induced death by promoting repair of potentially lethal DNA damage. These findings indicate that the overexpression of MUC1 can protect against IR-induced DNA DSBs and may represent a physiologic response that has been exploited by malignant cells.

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