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DNA修復分子XPBはヒト白血病癌遺伝子産物BCR-ABLとCDC24相同性領域を介して相互作用する：武田憲文¹、渋谷正史²、丸義朗²（¹東大医学部、²東大医科研　細胞遺伝）

The BCR-ABL oncoprotein potentially interacts with the xeroderma pigmentosum group B protein : Norifumi TAKEDA¹, Masabumi SHIBUYA², Yoshiro MARU² (¹Faculty of Med., Univ. Tokyo, ²Dept. of Genetics, Inst. Med. Sci., Univ. Tokyo)

The BCR-ABL oncogene is responsible for the pathogenesis of Philadelphia chromosome (Ph1)-positive human leukemias and is generated by a specific reciprocal translocation t(9; 22)(q34; q11). Depending on the locations of the breakpoint on the BCR genome, there are two alternative forms of BCR-ABL: P210 BCR-ABL found in chronic myelogenous leukemia (CML) and P185 BCR-ABL in acute lymphocytic leukemia (ALL). One of the unique clinical features in CML is that the chronic phase, which usually lasts for several years, is ultimately followed by transformation to an acute leukemic phase called blastic crisis. This transition is accompanied by additional genetic alterations in more than 80 % of the patients, suggesting that blastic crisis may be characterized by an intrinsic genomic instability. Although secondary mutations of specific genes like p53, Rb, p16, Ras, and AML-1 have been reported, there has been no consistent explanation for the molecular mechanisms which underlie this transformation process. Here we report that the xeroderma pigmentosum group B (XPB) protein was found to bind to P210 BCR-ABL through the previously uncharacterized CDC24 homology domain of BCR which is missing in P185 but is retained in P210 BCR-ABL. The binding ability between the CDC24 domain of BCR and the full-length XBP was 74 % of that observed in the well-known interaction between p53 and the SV40 large T antigen as measured by beta-galactosidase assay. This interaction impaired XPB-mediated cross-complementation of the repair deficiency in rodent ultraviolet (UV)-sensitive mutants of group 3. We propose that blastic crisis in CML may be induced by an analogous mechanism to the one which underlies the high predisposition to skin cancer in XPB patients.