Absence of caprin-1 results in defects in cellular proliferation.
Cytoplasmic activation/proliferation-associated protein-1 (Caprin-1) is a cytoplasmic phosphoprotein that is the prototype of a novel family of highly conserved proteins. Its levels, except in the brain, are tightly correlated with cellular proliferation. We disrupted caprin-1 alleles in the chicken B lymphocyte line DT40 using homologous recombination. We readily obtained clones with one disrupted allele (31% of transfectants), but upon transfection of heterozygous cells we obtained a 10-fold lower frequency of clones with disruption of the remaining allele. Clones of caprin-1-null DT40 cells exhibited marked reductions in their proliferation rate. To obviate the problem that we had selected for caprin-1-null clones with characteristics that partially compensated for the lack of Caprin-1, we generated clones of DT40 cells heterozygous for the caprin-1 gene in which, during disruption of the remaining wild-type allele of the chicken caprin-1 gene, the absence of endogenous Caprin-1 would be complemented by conditional expression of human Caprin-1. Suppression of expression of human Caprin-1 resulted in slowing of the proliferation rate, due to prolongation of the G1 phase of the cell cycle, formally demonstrating that Caprin-1 was essential for normal cellular proliferation.
Wang
Bin
B
The Biomedical Research Centre, University of British Columbia, Vancouver, British Columbia, Canada.
David
Muriel D
MD
Schrader
John W
JW
D000595:Amino Acid Sequence; D000818:Animals; D018797:Cell Cycle Proteins / Q000096:biosynthesis / Q000235:genetics*; D002460:Cell Line; D049109:Cell Proliferation; D002645:Chickens; D017124:Conserved Sequence; D018076:DNA, Complementary / Q000235:genetics; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D016193:G1 Phase / Q000235:genetics; D018390:Gene Targeting; D006801:Humans; D051379:Mice; D008969:Molecular Sequence Data; D010750:Phosphoproteins / Q000172:deficiency / Q000235:genetics*; D010766:Phosphorylation; D016415:Sequence Alignment; D014162:Transfection
C486562:CAPRIN1 protein, human; D018797:Cell Cycle Proteins; D018076:DNA, Complementary; D010750:Phosphoproteins; D048049:Extracellular Signal-Regulated MAP Kinases