Division of Radiation Cancer Research, Korea Institute of Radiological & Medical Sciences, Seoul 139-706, Republic of Korea.
Biochem Biophys Res Commun. 2012 Aug 10;424(4):681-6. doi: 10.1016/j.bbrc.2012.07.006. Epub 2012 Jul 10.
Upon apoptotic stimulation, glyceraldehyde-3-phosphate dehydrogenase (GAPDH), a cytosolic enzyme normally active in glycolysis, translocates into the nucleus and activates an apoptotic cascade therein. In the present work, we show that SIRT1 prevents nuclear translocation of GAPDH via interaction with GAPDH. SIRT1 depletion triggered nuclear translocation of cytosolic GAPDH even in the absence of apoptotic stress. Such translocation was not, however, observed when SIRT1 enzymatic activity was inhibited, indicating that SIRT1 protein per se, rather than the deacetylase activity of the protein, is required to inhibit GAPDH translocation. Upon irradiation, SIRT1 prevented irradiation-induced nuclear translocation of GAPDH, accompanied by interaction of SIRT1 and GAPDH. Thus, SIRT1 functions to retain GAPDH in the cytosol, protecting the enzyme from nuclear translocation via interaction with these two proteins. This serves as a mechanism whereby SIRT1 regulates cell survival upon induction of apoptotic stress by means that include irradiation.
在凋亡刺激下，甘油醛-3-磷酸脱氢酶（GAPDH），一种通常在糖酵解中活跃的细胞质酶，易位到细胞核内并激活其中的凋亡级联反应。在本工作中，我们表明 SIRT1 通过与 GAPDH 相互作用防止 GAPDH 的核易位。即使在没有凋亡应激的情况下，SIRT1 的耗竭也会触发细胞质 GAPDH 的核易位。然而，当抑制 SIRT1 的酶活性时，并没有观察到这种易位，这表明 SIRT1 蛋白本身，而不是该蛋白的去乙酰化酶活性，是抑制 GAPDH 易位所必需的。照射后，SIRT1 阻止了照射诱导的 GAPDH 核易位，同时伴随着 SIRT1 和 GAPDH 的相互作用。因此，SIRT1 通过与这两种蛋白的相互作用将 GAPDH 保留在细胞质中，从而防止酶的核易位。这是一种机制，通过这种机制，SIRT1 可以在诱导凋亡应激时通过包括照射在内的方式来调节细胞存活。
