期刊
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
卷 337, 期 4, 页码 1176-1184出版社
ACADEMIC PRESS INC ELSEVIER SCIENCE
DOI: 10.1016/j.bbrc.2005.09.177
关键词
proteomics; alkylation DNA damage; MGMT; O-6-alkylguanine-DNA alkyltransferase; DNA repair; protein-protein interactions; cancer chemotherapy; cell cycle; replication; mass spectrometry
资金
- NCI NIH HHS [R01 CA97343] Funding Source: Medline
Recent evidence suggests that human O-6-methylguanine-DNA methyltransferase (MGMT), a DNA repair protein that protects the genome against mutagens and accords tumor resistance to many anticancer alkylating agents, may have other roles besides repair. Therefore, we isolated MGMT-interacting proteins from extracts of HT29 human colon cancer cells using affinity chromatography on MGMT-Sepharose. Specific proteins bound to this column were identified by electrospray ionization tandem mass spectrometry and/or Western blotting. These procedures identified > 60 MGMT-interacting proteins with diverse functions including those involved in DNA replication and repair (MCM2, PCNA, ORC1, DNA polymerase 6, MSH-2, and DNA-dependent protein kinase), cell cycle progression (CDK1, cyclin 13, CDK2, CDC7, CDC10, 14-3-3 protein, and p21(waf1/cip1)), RNA processing and translation (poly(A)-binding protein, nucleolin, heterogeneous nuclear ribonucleoproteins, A2/B1, and elongation factor-lot), several histories (H4, H3.4, and H2A.1), and topoisomerase 1. The heat shock proteins, HSP-90 alpha and P, also bound strongly with MGMT. The DNA repair activity of MGMT was greatly enhanced in the presence of interacting proteins or histones. These data, for the first time, suggest that human MGMT is likely to have additional functions, possibly, in sensing and integrating the DNA damage/repair-related signals with replication, cell cycle progression, and genomic stability. (c) 2005 Elsevier Inc. All rights reserved.
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