BCR/ABL regulates mammalian RecA homologs, resulting in drug resistance Journal Article
| Authors: | Slupianek, A.; Schmutte, C.; Tombline, G.; Nieborowska-Skorska, M.; Hoser, G.; Nowicki, M. O.; Pierce, A. J.; Fishel, R.; Skorski, T. |
| Article Title: | BCR/ABL regulates mammalian RecA homologs, resulting in drug resistance |
| Abstract: | RAD51 is one of six mitotic human homologs of the E. coli RecA protein (RAD51-Paralogs) that play a central role in homologous recombination and repair of DNA double-strand breaks (DSBs). Here we demonstrate that RAD51 is important for resistance to cisplatin and mitomycin C in cells expressing the BCR/ABL oncogenic tyrosine kinase. BCR/ABL significantly enhances the expression of RAD51 and several RAD51-Paralogs. RAD51 overexpression is mediated by a STAT5-dependent transcription as well as by inhibition of caspase-3-dependent cleavage. Phosphorylation of the RAD51 Tyr-315 residue by BCR/ABL appears essential for enhanced DSB repair and drug resistance. Induction of the mammalian RecA homologs establishes a unique mechanism for DNA damage resistance in mammalian cells transformed by an oncogenic tyrosine kinase. |
| Keywords: | controlled study; protein expression; protein phosphorylation; human cell; dna-binding proteins; cisplatin; nonhuman; antineoplastic agents; animal cell; mammalia; bone marrow cells; dna repair; apoptosis; enzyme inhibition; protein degradation; cell line; caspase 3; enzyme activation; drug resistance; enzyme activity; caspases; chronic myeloid leukemia; phosphorylation; animalia; dna strand breakage; antibiotic resistance; enzyme regulation; transcription regulation; protein induction; mitomycin c; microscopy, fluorescence; genes, reporter; trans-activators; bcr abl protein; antibiotics, antineoplastic; mitomycin; monkey; stat5 transcription factor; fusion proteins, bcr-abl; rad51 protein; rad51 recombinase; cricetinae; reca protein; rec a recombinases; hamster; interleukin-3; trans-activation (genetics); milk proteins; humans; human; article; methylnitronitrosoguanidine |
| Journal Title: | Molecular Cell |
| Volume: | 8 |
| Issue: | 4 |
| ISSN: | 1097-2765 |
| Publisher: | Cell Press |
| Date Published: | 2001-10-26 |
| Start Page: | 795 |
| End Page: | 806 |
| Language: | English |
| DOI: | 10.1016/s1097-2765(01)00357-4 |
| PUBMED: | 11684015 |
| PROVIDER: | scopus |
| DOI/URL: | |
| Notes: | Export Date: 21 May 2015 -- Source: Scopus |
