Downregulation of Repressive CUP/AP-2 Isoforms during Adipocyte Differentiation

• Published in: Biochemical and biophysical research communications 2001-11, Vol.288 (4), p.752-756
• Main Authors: Holt, Elizabeth H., Lane, M.Daniel
• Format: Article
• Language: English
• Subjects: 3T3-L1 preadipocytes; AAP-2^a protein; Adipocytes - cytology; Adipocytes - metabolism; Animals; C/EBP^a protein; C/EBPα undifferentiated protein (CUP); CCAAT enhancer binding protein (C/EBP); CCAAT-Enhancer-Binding Protein-alpha - genetics; Cell Differentiation; Cell Line; CUP protein; DNA-Binding Proteins - genetics; Down-Regulation; Mice; Mice, Inbred C57BL; Nuclease Protection Assays; Protein Isoforms - genetics; Repressor Proteins - genetics; Response Elements - genetics; RNA, Messenger - genetics; RNA, Messenger - metabolism; Stem Cells - cytology; Transcription Factor AP-2; Transcription Factors - genetics
• ISSN: 0006-291X; 1090-2104
• DOI: 10.1006/bbrc.2001.5846

Activation of transcription of the C/EBPα (CCAAT/enhancer binding protein α) gene is a critical event in the differentiation of 3T3-L1 preadipocytes into adipocytes. The kinetics of this process parallels a decline of AP-2α protein (also referred to as CUP, C/EBP undifferentiated protein) and decreased binding of CUP/AP-2α to the C/EBPα promoter. Mutation of the CUP/AP-2 binding sites in the C/EBPα promoter results in increased C/EBPα expression. Based on these findings, it appears that decline in AP-2α expression is an important early event in the adipocyte differentiation program. In the studies presented here, we identify three mRNAs that encode the repressive CUP/AP-2α isoforms expressed in undifferentiated 3T3-L1 preadipocytes. We demonstrate that the kinetics of the decline of these isoforms' expression over the course of differentiation parallels both the decrease in CUP/AP-2α DNA binding activity and the increase in C/EBPα protein observed in previous studies.