Zangen Rachel, Ratovitski Edward, Sidransky David
Department of Otolaryngology/Head and Neck Surgery, The Johns Hopkins University School of Medicine, Baltimore, Maryland 21205, USA.
Cell Cycle. 2005 Oct;4(10):1313-5. doi: 10.4161/cc.4.10.2066. Epub 2005 Oct 1.
After exposure to damaging agents, the p53 tumor suppressor is stabilized mediating cell cycle arrest and apoptosis. p53 family member, DeltaNp63 promotes cell proliferation and accelerates tumor growth. We previously found that the genotoxic stress agents induced a decrease of DeltaNp63alpha. We further observed that genotoxic stress mediated phosphorylation of DeltaNp63alpha targeting it into proteasome degradation. Here, we found that high DeltaNp63 protein levels in primary tumors accurately predicted response to platinum based chemotherapy and a favorable outcome in head and neck cancer patients. Our data suggest that degradation of DeltaNp63alpha is part of the cellular response to DNA damage in head and neck cancers. The findings may have implications for the rational use of DNA damaging agents in human cancer.
在接触损伤因子后，p53肿瘤抑制蛋白被稳定化，介导细胞周期停滞和凋亡。p53家族成员DeltaNp63促进细胞增殖并加速肿瘤生长。我们之前发现基因毒性应激因子可诱导DeltaNp63α水平降低。我们进一步观察到基因毒性应激介导DeltaNp63α磷酸化，使其靶向蛋白酶体降解。在此，我们发现原发性肿瘤中DeltaNp63蛋白水平高可准确预测头颈癌患者对铂类化疗的反应及良好预后。我们的数据表明，DeltaNp63α的降解是头颈癌中细胞对DNA损伤反应的一部分。这些发现可能对人类癌症中DNA损伤剂的合理使用具有启示意义。
