SIRT1 interacts with and protects glyceraldehyde-3-phosphate dehydrogenase (GAPDH) from nuclear translocation: implications for cell survival after irradiation.
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.
Division of Radiation Cancer Research, Korea Institute of Radiological & Medical Sciences, Seoul 139-706, Republic of Korea.
Hyun-Yoo
HY
Joo
Seon Rang
SR
Woo
Yan-Nan
YN
Shen
Mi Yong
MY
Yun
Hyun-Jin
HJ
Shin
Eun-Ran
ER
Park
Su-Hyeon
SH
Kim
Jeong-Eun
JE
Park
Yeun-Jin
YJ
Ju
Sung Hee
SH
Hong
Sang-Gu
SG
Hwang
Myung-Haing
MH
Cho
Joon
J
Kim
Kee-Ho
KH
Lee
D021581:Active Transport, Cell Nucleus; D017209:Apoptosis / Q000502:physiology* / Q000528:radiation effects; D002467:Cell Nucleus / Q000201:enzymology*; D002470:Cell Survival / Q000528:radiation effects; D003600:Cytosol / Q000201:enzymology; D024581:Glyceraldehyde-3-Phosphate Dehydrogenase (Phosphorylating) / Q000378:metabolism*; D006367:HeLa Cells; D006801:Humans; D034741:RNA, Small Interfering / Q000235:genetics; D011836:Radiation Tolerance; D056566:Sirtuin 3 / Q000235:genetics / Q000378:metabolism*
D034741:RNA, Small Interfering; D024581:Glyceraldehyde-3-Phosphate Dehydrogenase (Phosphorylating); C466093:SIRT3 protein, human; D056566:Sirtuin 3