Cheung K-John, Li Gang
Division of Dermatology, Department of Medicine, University of British Columbia, Vancouver Hospital and Health Sciences Centre, Vancouver, British Columbia, V6H 3Z6, Canada.
Exp Cell Res. 2002 Oct 1;279(2):291-8. doi: 10.1006/excr.2002.5610.
The biological functions of the tumor suppressor ING1 have been studied extensively in the past few years since it was cloned. It shares many biological functions with p53 and has been reported to mediate growth arrest, senescence, apoptosis, anchorage-dependent growth, chemosensitivity, and DNA repair. Some of these functions, such as cell cycle arrest and apoptosis, have been shown to be dependent on the activity of both ING1 and p53 proteins. Two recent reports by Scott and colleagues demonstrate that p33(ING1) (one of the ING1 isoforms) translocates to the nucleus and binds to PCNA upon UV irradiation. Here we report that p33(ING1) mediates UV-induced cell death in melanoma cells. We found that overexpression of p33(ING1) increased while the introduction of an antisense p33(ING1) plasmid reduced the apoptosis rate in melanoma cells after UVB irradiation. We also demonstrated that enhancement of UV-induced apoptosis by p33(ING1) required the presence of p53. Moreover, we found that p33(ING1) enhanced the expression of endogenous Bax and altered the mitochondrial membrane potential. Taken together, these observations strongly suggest that p33(ING1) cooperates with p53 in UVB-induced apoptosis via the mitochondrial cell death pathway in melanoma cells.
肿瘤抑制因子ING1自被克隆以来，其生物学功能在过去几年中得到了广泛研究。它与p53具有许多共同的生物学功能，据报道可介导生长停滞、衰老、凋亡、锚定依赖性生长、化学敏感性和DNA修复。其中一些功能，如细胞周期停滞和凋亡，已被证明依赖于ING1和p53蛋白的活性。斯科特及其同事最近的两篇报道表明，p33(ING1)（ING1的一种亚型）在紫外线照射后会转移至细胞核并与增殖细胞核抗原（PCNA）结合。在此我们报道p33(ING1)介导黑色素瘤细胞中紫外线诱导的细胞死亡。我们发现，p33(ING1)的过表达会增加，而导入反义p33(ING1)质粒则会降低紫外线B照射后黑色素瘤细胞的凋亡率。我们还证明，p33(ING1)增强紫外线诱导的凋亡需要p53的存在。此外，我们发现p33(ING1)增强了内源性Bax的表达并改变了线粒体膜电位。综上所述，这些观察结果强烈表明，p33(ING1)在黑色素瘤细胞中通过线粒体细胞死亡途径与p53协同作用，介导紫外线B诱导的凋亡。
