S-Space College of Medicine/School of Medicine (의과대학/대학원) Anatomy (해부학전공) Journal Papers (저널논문_해부학전공)
p34(SEI-1) Inhibits Doxorubicin-Induced Senescence through a Pathway Mediated by Protein Kinase C-δ and c-Jun-NH(2)-Kinase 1 Activation in Human Breast Cancer MCF7 Cells
- Lee, Sae Lo Oom; Hong, Seung-Woo; Shin, Jae-Sik; Kim, Jin Sun; Hong, Nam-Joo; Lee, Wang-Jae; Lee, Myeong-Sok; Jin, Dong-Hoon; Kim, Dae Jin; Ko, Seong-Gyu
- Issue Date
- AMER ASSOC CANCER RESEARCH
- MOLECULAR CANCER RESEARCH; Vol.7(11); 1845-1853
- In this study, we describe a novel function of the p34(SEI-1) protein, which is both an oncogenic protein and a positive regulator of the cell cycle. The p34(SEI-1) protein was found to inhibit doxorubicin-induced senescence. We investigated the molecular mechanisms of the inhibitory effect of p34(SEI-1) on senescence. First, we found that the activation of protein kinase C-delta (PKC-delta), which is cleaved into a 38 kDa active form from a 78 kDa pro-form, induced after doxorubicin treatment, was inhibited by p34(SEI-1). Furthermore, p34(SEI-1) induced the ubiquitination of PKC-delta. Yet, there is no interaction between p34(SEI-1) and PKC-delta. We also found that the phosphorylation of c-Jun-NH(2)-kinase 1 (JNK1) induced after doxorubicin treatment was suppressed by p34(SEI-1), but not in JNK2. Consistently, pharmacologic or genetic inactivation of either PKC-delta or JNK1 was found to inhibit doxorubicin-induced senescence. In addition, the genetic inactivation of PKC-delta by PKC-delta small interfering RNA resulted in an inhibition of JNK1 activation, but PKC-delta expression was not inactivated by JNK1 small interfering RNA, implying that the activation of JNK1 could be dependently induced by PKC-delta. Therefore, p34(SEI-1) inhibits senescence by inducing PKC-delta ubiquitination and preventing PKC-delta-dependent phosphorylation of JNK1.
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