O'Rourke J, Yuan R, DeWille J
Ohio State University Biochemistry Program, Ohio State University, Columbus, Ohio 43210, USA.
J Biol Chem. 1997 Mar 7;272(10):6291-6. doi: 10.1074/jbc.272.10.6291.
CCAAT/enhancer binding proteins (C/EBPs) are a highly conserved family of DNA-binding proteins that regulate cell growth and differentiation in a highly tissue-specific manner. These experiments investigated the influence of the cell cycle on C/EBP isoform expression in mammary epithelial cells (COMMA D) and fibroblasts (NIH3T3). C/EBP-delta gene expression is induced in COMMA D cells arrested in G0 by serum and growth factor withdrawal or contact inhibition. C/EBP-delta mRNA, nuclear protein content, and DNA binding activity increase during G0 growth arrest and decrease after cell cycle induction in COMMA D cells. Growth arrest is markedly delayed in COMMA D cells expressing a C/EBP-delta antisense construct. C/EBP-beta is induced during G1 of the cell cycle. In contrast to COMMA D cells, C/EBP-beta and C/EBP-delta mRNA levels remain relatively constant in growth-arrested and cell cycle-induced NIH3T3 cells. However, C/EBP homologous protein (CHOP10) mRNA levels markedly increase in growth-arrested NIH3T3 cells. Both COMMA D and NIH3T3 cells express growth arrest-specific (gas1) and JunD during G0. These results demonstrate that COMMA D and NIH3T3 cells achieve a common growth arrest (G0) state by cell-specific strategies that involve the induction of different C/EBP isoforms.
CCAAT/增强子结合蛋白（C/EBPs）是一类高度保守的DNA结合蛋白家族，它们以高度组织特异性的方式调节细胞生长和分化。这些实验研究了细胞周期对乳腺上皮细胞（COMMA D）和成纤维细胞（NIH3T3）中C/EBP异构体表达的影响。通过血清和生长因子撤除或接触抑制使COMMA D细胞停滞在G0期时，可诱导C/EBP-δ基因表达。在COMMA D细胞中，G0期生长停滞期间C/EBP-δ mRNA、核蛋白含量和DNA结合活性增加，细胞周期诱导后则降低。在表达C/EBP-δ反义构建体的COMMA D细胞中，生长停滞明显延迟。细胞周期的G1期可诱导C/EBP-β。与COMMA D细胞不同，在生长停滞和细胞周期诱导的NIH3T3细胞中，C/EBP-β和C/EBP-δ mRNA水平保持相对恒定。然而，在生长停滞的NIH3T3细胞中，C/EBP同源蛋白（CHOP10）mRNA水平显著增加。COMMA D细胞和NIH3T3细胞在G0期均表达生长停滞特异性蛋白（gas1）和JunD。这些结果表明，COMMA D细胞和NIH3T3细胞通过涉及诱导不同C/EBP异构体的细胞特异性策略实现共同的生长停滞（G0）状态。
