Parcs is a dual regulator of cell proliferation and apaf-1 function.
Here we identify a novel protein, named Parcs for pro-apoptotic protein required for cell survival, that is involved in both cell cycle progression and apoptosis. Parcs interacted with Apaf-1 by binding to the oligomerization domain of Apaf-1. Apaf-1-mediated activation of caspase-9 and caspase-3 was markedly decreased in a cytosolic fraction isolated from HeLa cells with reduced parcs expression. Interestingly, parcs deficiency blocked cell proliferation in non-tumorigenic cells but not in multiple tumor cell lines. In MCF-10A cells, parcs deficiency led to early G1 arrest. Conditional inactivation of parcs in genetically modified primary mouse embryonic fibroblasts using the Cre-LoxP system also resulted in the inhibition of cell proliferation. We conclude that Parcs may define a molecular checkpoint in the control of cell proliferation for normal cells that is lost in tumor cells.
Department of Cell Biology, Harvard Medical School, Boston, Massachusetts 02115, USA.
Roberto
R
Sanchez-Olea
Sara
S
Ortiz
Odmara
O
Barreto
Qing
Q
Yang
Chi-jie
CJ
Xu
Hong
H
Zhu
Junying
J
Yuan
D000818:Animals; D053477:Apoptotic Protease-Activating Factor 1 / Q000235:genetics / Q000378:metabolism*; D053148:Caspase 3 / Q000235:genetics / Q000378:metabolism; D053453:Caspase 9 / Q000235:genetics / Q000378:metabolism; D018797:Cell Cycle Proteins / Q000235:genetics / Q000378:metabolism*; D016193:G1 Phase / Q000502:physiology*; D006367:HeLa Cells; D006801:Humans; D051379:Mice; D018345:Mice, Knockout; D017434:Protein Structure, Tertiary / Q000502:physiology
C506593:Apaf1 protein, mouse; D053477:Apoptotic Protease-Activating Factor 1; D018797:Cell Cycle Proteins; C505409:Casp3 protein, mouse; D053148:Caspase 3; D053453:Caspase 9