C/EBPα Regulation of the Growth-Arrest-Associated Gene gadd45

Autor: J I Morgan, Cara M. Constance, R M Umek
Rok vydání: 1996
Předmět:
Chloramphenicol O-Acetyltransferase
Transcriptional Activation
Cell cycle checkpoint
Immunoprecipitation
Cellular differentiation
Molecular Sequence Data
Genes
myc
Biology
Transfection
Polymerase Chain Reaction
Proto-Oncogene Mas
Proto-Oncogene Proteins c-myc
Mice
chemistry.chemical_compound
Adipocyte
Adipocytes
Animals
Humans
Promoter Regions
Genetic
Molecular Biology
Transcription factor
DNA Primers
Leucine Zippers
Base Sequence
Ccaat-enhancer-binding proteins
Gadd45
Intracellular Signaling Peptides and Proteins
Nuclear Proteins
Proteins
Cell Differentiation
3T3 Cells
Cell Biology
Genes
p53
Molecular biology
Recombinant Proteins
DNA-Binding Proteins
chemistry
Protein Biosynthesis
CCAAT-Enhancer-Binding Proteins
Tumor Suppressor Protein p53
DNA Probes
DNA Damage
Transcription Factors
Research Article
Zdroj: Molecular and Cellular Biology. 16:3878-3883
ISSN: 1098-5549
DOI: 10.1128/mcb.16.7.3878
Popis: CCAAT/enhancer-binding protein alpha (C/EBPalpha) is expressed in postmitotic, differentiated adipocytes and is required for adipose conversion of 3T3-L1 cells in culture. Temporal misexpression of C/EBPalpha in undifferentiated adipoblasts leads to mitotic growth arrest. We report here that growth arrest- and DNA damage-inducible gene 45 (gadd45) is preferentially expressed in differentiated 3T3-L1 adipocytes similar to phenotype-associated genes. Furthermore, C/EBPalpha transactivates a reporter plasmid containing 1.5 kb of the gadd45 promoter region. The proto-oncogene myc, which inhibits adipocyte differentiation, abrogates C/EBPalpha activation of gadd45. gadd45 is known to be a target of the tumor suppressor p53 in a G1 checkpoint activated by DNA damage. Immunoprecipitation of radiolabeled proteins with conformation-specific antibodies revealed that wild-type p53 is expressed throughout 3T3-L1 adipocyte development, including the postmitotic period characterized by the accumulation of gadd45 and C/EBPalpha. A stable 3T3-L1 subline was engineered to express a dominant negative p53, human p53(143ala). The p53(143ala) subline differentiated to adipocytes and showed appropriate developmental expression of gadd45. These findings suggest that postmitotic growth arrest is coupled to adipocyte differentiation via C/EBPalpha stimulation of growth arrest-associated and phenotype-associated genes.
Databáze: OpenAIRE
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