C/EBPalphap30 plays transcriptional regulatory roles distinct from C/EBPalphap42.
CCAAT/enhancer binding protein alpha (C/EBPalpha) is a transcriptional regulatory factor that inhibits cell proliferation, and alternative translational initiation produces two polypeptides, C/EBPalphap30 and C/EBPalphap42. By expression profiling, it was revealed that C/EBPalphap30 specifically inhibited a unique set of genes, including MPP11, p84N5 and SMYD2, which were not affected by C/EBPalphap42 in both QSG-7701 hepatocyte cell line and QGY-7703 hepatoma cells. Semi-quantitative RT-PCR analysis independently confirmed these results. Chromatin immunoprecipitation assay showed that C/EBPalphap30 bound to the promoters of these genes more strongly than C/EBPalphap42. In clinical hepatoma samples in which C/EBPalpha was downregulated, all three genes specifically inhibited by C/EBPalphap30 were upregulated. However, repression of MPP11, p84N5 and SMYD2 genes might not be directly involved in C/EBPalphap30-mediated growth inhibition. Our data suggest that C/EBPalphap30 regulates a unique set of target genes and is more than a dominant-negative regulator of C/EBPalphap42.
Wang
Chunxi
C
State Key Laboratory of Molecular Biology, Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Graduate School of the Chinese Academy of Sciences, Shanghai 200031, China.
Chen
Xiaotao
X
Wang
Yanping
Y
Gong
Jialei
J
Hu
Gengxi
G
D022763:CCAAT-Enhancer-Binding Protein-alpha / Q000235:genetics / Q000502:physiology*; D002460:Cell Line; D005786:Gene Expression Regulation; D006801:Humans; D011401:Promoter Regions, Genetic; D020033:Protein Isoforms / Q000235:genetics / Q000502:physiology
D022763:CCAAT-Enhancer-Binding Protein-alpha; D020033:Protein Isoforms