Cell-cycle-dependent PC-PLC regulation by APC/C(Cdc20)-mediated ubiquitin-proteasome pathway.
Phosphatidylcholine-specific phospholipase C (PC-PLC) is involved in the cell signal transduction, cell proliferation, and apoptosis. The mechanism of its action, however, has not been fully understood, particularly, the role of PC-PLC in the cell cycle. In the present study, we found that cell division cycle 20 homolog (Cdc20) and PC-PLC were co-immunoprecipitated reciprocally by either antibody in rat hepatoma cells CBRH-7919 as well as in rat liver tissue. Using confocal microscopy, we found that PC-PLC and Cdc20 were co-localized in the perinuclear endoplasmic reticulum region (the "juxtanuclear quality control" compartment, JUNQ). The expression level and activities of PC-PLC changed in a cell-cycle-dependent manner and were inversely correlated with the expression of Cdc20. Intriguingly, Cdc20 overexpression altered the subcellular localization and distribution of PC-PLC, and caused PC-PLC degradation by the ubiquitin proteasome pathway (UPP). Taken together, our data indicate that PC-PLC regulation in cell cycles is controlled by APC/C(Cdc20)-mediated UPP.
Department of Biochemistry, Fudan University, Shanghai, PR China.
Da
D
Fu
Yushui
Y
Ma
Wei
W
Wu
Xuchao
X
Zhu
Chengyou
C
Jia
Qianlei
Q
Zhao
Chunyi
C
Zhang
Xing Zhong
XZ
Wu
D000818:Animals; D019556:COS Cells; D064199:Cdc20 Proteins; D002453:Cell Cycle; D018797:Cell Cycle Proteins / Q000032:analysis / Q000502:physiology*; D002460:Cell Line; D002522:Chlorocebus aethiops; D004721:Endoplasmic Reticulum / Q000737:chemistry; D008099:Liver / Q000737:chemistry; D046988:Proteasome Endopeptidase Complex / Q000378:metabolism*; D051381:Rats; D010738:Type C Phospholipases / Q000032:analysis / Q000378:metabolism*; D025801:Ubiquitin / Q000378:metabolism*
D064199:Cdc20 Proteins; C577494:Cdc20 protein, rat; D018797:Cell Cycle Proteins; D025801:Ubiquitin; D010738:Type C Phospholipases; C105598:phosphatidylcholine-specific phospholipase C; D046988:Proteasome Endopeptidase Complex