ERK mediates anti-apoptotic effect through phosphorylation and cytoplasmic localization of p21Waf1/Cip1/Sdi in response to DNA damage in normal human embryonic fibroblast (HEF) cells.
Since anti-apoptotic effect of ERK has not been elucidated clearly in DNA-damage-induced cell death, the role of ERK was examined in normal HEF cells treated with mild DNA damage using etoposide or camptothecin. ERK was activated by DNA damage in HEF cells. PD98059 increased apoptosis and reduced DNA-damage-induced p21Waf1/Cip1/Sdi level. Depletion of p21Waf1/Cip1/Sdi induced cell death and PD98059 induced additional cell death. DNA-damage-induced increase in cytoplasmic localization and phosphorylation of threonine residues of p21Waf1/Cip1/Sdi was reversed by PD98059. Thus, the results suggest that ERK pathway mediates anti-apoptotic effects through phosphorylation and cytoplasmic localization of p21Waf1/Cip1/Sdi in response to mild DNA damage.
Department of Biochemistry, College of Medicine, Hallym University, 1 Okchon-dong Chuncheon, Gangwon-do, 200-702, Republic of Korea.
Jee-In
JI
Heo
Soo-Jin
SJ
Oh
Yoon-Jung
YJ
Kho
Jeong-Hyeon
JH
Kim
Hong-Joon
HJ
Kang
Seong-Hoon
SH
Park
Hyun-Seok
HS
Kim
Jong-Yeon
JY
Shin
Min-Ju
MJ
Kim
Sung Chan
SC
Kim
Jae-Bong
JB
Park
Jaebong
J
Kim
Jae-Yong
JY
Lee
D017209:Apoptosis / Q000502:physiology*; D015153:Blotting, Western; D053148:Caspase 3 / Q000378:metabolism; D002458:Cell Fractionation; D002460:Cell Line; D050759:Cyclin-Dependent Kinase Inhibitor p21 / Q000378:metabolism*; D003593:Cytoplasm / Q000378:metabolism*; D004249:DNA Damage; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism*; D005434:Flow Cytometry; D006801:Humans; D047468:Immunoprecipitation; D010766:Phosphorylation; D013778:Tetrazolium Salts; D013844:Thiazoles
C493956:CDKN1A protein, human; D050759:Cyclin-Dependent Kinase Inhibitor p21; D013778:Tetrazolium Salts; D013844:Thiazoles; D048049:Extracellular Signal-Regulated MAP Kinases; D053148:Caspase 3; C022616:thiazolyl blue