PKB phosphorylation and survivin expression are cooperatively regulated by disruption of microfilament cytoskeleton.
Changes in cell shape can lead to detachment and cell death, and the disruption in the actin cytoskeletal network, as one marker of cell shape changes, can itself induce apoptosis. In this study, the effects of cytochalasin B on the apoptosis-related proteins, protein kinase B and survivin were investigated. Apoptosis induced by disruption of microfilaments with cytochalasin B was found, although it happened at a low level, to simultaneously occur with G2/M arrest in 50% of the cytochalasin B-treated cells. During apoptosis, PKB phosphorylation and survivin expression were decreased by cytochalasin B, and the decline in survivin expression was preceded by PKB dephosphorylation, which implicated that survivin may be a target of PKB protein. The G2/M arrest of cytochalasin B-treated cells may be the direct function of cytochalasin B to microfilaments or the subsequent inhibition of survivin expression, or both. These results suggest that PKB/survivin signaling pathway may be responsible for the apoptosis induced by the disruption of actin cytoskeleton.
Liang
Yu-Long
YL
Department of Biochemistry and Molecular Biology, Shanghai Medical College, Fudan University, Shanghai, PR China.
Wang
Li-Ying
LY
Wu
Heng
H
Ma
Dong-Zhu
DZ
Xu
Zhen
Z
Zha
Xi-Liang
XL
D000199:Actins / Q000378:metabolism; D017209:Apoptosis; D015153:Blotting, Western; D002453:Cell Cycle; D045744:Cell Line, Tumor; D003571:Cytochalasin B / Q000378:metabolism / Q000494:pharmacology; D003599:Cytoskeleton / Q000378:metabolism*; D015536:Down-Regulation; D016195:G2 Phase; D015971:Gene Expression Regulation, Enzymologic; D006801:Humans; D020287:In Situ Nick-End Labeling; D051034:Inhibitor of Apoptosis Proteins; D008869:Microtubule-Associated Proteins / Q000096:biosynthesis* / Q000378:metabolism; D008938:Mitosis; D009363:Neoplasm Proteins; D010766:Phosphorylation; D017346:Protein Serine-Threonine Kinases / Q000096:biosynthesis* / Q000378:metabolism / Q000494:pharmacology; D011518:Proto-Oncogene Proteins / Q000096:biosynthesis* / Q000378:metabolism / Q000494:pharmacology; D051057:Proto-Oncogene Proteins c-akt; D015398:Signal Transduction; D000077022:Survivin; D013997:Time Factors
D000199:Actins; C107489:BIRC5 protein, human; D051034:Inhibitor of Apoptosis Proteins; D008869:Microtubule-Associated Proteins; D009363:Neoplasm Proteins; D011518:Proto-Oncogene Proteins; D000077022:Survivin; D003571:Cytochalasin B; D017346:Protein Serine-Threonine Kinases; D051057:Proto-Oncogene Proteins c-akt