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A 30-kDa alternative translation product of the CCAAT/enhancer binding protein alpha message: transcriptional activator lacking antimitotic activity.
Open accessAbstract
Full-length (42 kDa) CCAAT/enhancer binding protein alpha (C/EBP alpha) (p42) has been implicated in the transcriptional activation of adipocyte genes including the 422(aP2) and C/EBP alpha genes during differentiation of 3T3-L1 preadipocytes. We have identified a 30-kDa isoform (p30) of C/EBP alpha that is expressed by 3T3-L1 adipocytes, mouse adipose tissue, and rat liver. In vitro translation of wild-type C/EBP alpha mRNA or transient transfection with a wild-type C/EBP alpha vector gave rise to similar levels of p42 and p30. Mutational analysis revealed that p30 is an alternative translation product initiated at the third in-frame methionine codon of the C/EBP alpha message. p30C/EBP alpha binds to the C/EBP sites within and activates reporter gene expression driven by the 422(aP2) and C/EBP alpha gene promoters. Although transfection of 3T3-L1 preadipocytes with a strong p30C/EBP alpha expression vector is insufficient to induce differentiation, this vector advances the differentiation program. Unlike p42C/EBP alpha, which inhibits cell proliferation, p30C/EBP alpha is not antimitotic. Thus, the N-terminal 12-kDa segment of full-length C/EBP alpha contains an amino acid sequence necessary for antimitotic activity. During differentiation of 3T3-L1 preadipocytes and during hepatocyte development, the cellular p42C/EBP alpha/p30C/EBP alpha ratio changes, raising the possibility of a regulatory role.
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Citations
Cites
CCAAT-Enhancer Binding Protein: A Component of a Differentiation Switch
Umek, R. M., Friedman, A. D., & McKnight, S. L. (1991) · Science · doi:10.1126/science.1987644 · Cited by 712
Birkenmeier, E. H., Gwynn, B., Howard, S., Jerry, J., Gordon, J. I., Landschulz, W. H., & McKnight, S. L. (1989) · Genes & Development · doi:10.1101/gad.3.8.1146 · Cited by 613
Cited by
Ingolia, N. T., Lareau, L. F., & Weissman, J. S. (2011) · Cell · doi:10.1016/j.cell.2011.10.002 · Cited by 2,187
Pabst, T., Mueller, B. U., Zhang, P., Radomska, H. S., Narravula, S., Schnittger, S., Behre, G., Hiddemann, W., & Tenen, D. G. (2001) · Nature Genetics · doi:10.1038/85820 · Cited by 901
Biological Role of the CCAAT/Enhancer-binding Protein Family of Transcription Factors
Lekstrom-Himes, J., & Xanthopoulos, K. G. (1998) · Journal of Biological Chemistry · doi:10.1074/jbc.273.44.28545 · Cited by 801
Upstream Open Reading Frames as Regulators of mRNA Translation
Morris, D. R., & Geballe, A. P. (2000) · Molecular and Cellular Biology · doi:10.1128/mcb.20.23.8635-8642.2000 · Cited by 736
CONTROL OF TRANSLATION INITIATION IN ANIMALS
Gray, N. K., & Wickens, M. (1998) · Annual Review of Cell and Developmental Biology · doi:10.1146/annurev.cellbio.14.1.399 · Cited by 503
Metadata
- Authors
- Lin, F. T., MacDougald, O. A., Diehl, A. M., & Lane, M. D.
- Venue
- Proceedings of the National Academy of Sciences
- Published
- 1993-10-15
- Volume
- 90
- Issue
- 20
- Pages
- 9606-9610
- ISSN
- 0027-8424 (ISSN-L)
- 1091-6490
- OpenAlex
- W2020649739
- Cited by
- 319
- References
- 2
- FWCI
- 5.12
- Type
- journal article
- Language
- en
- Open access
- green
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- Lin, F. T., MacDougald, O. A., Diehl, A. M., & Lane, M. D. (1993). A 30-kDa alternative translation product of the CCAAT/enhancer binding protein alpha message: transcriptional activator lacking antimitotic activity. Proceedings of the National Academy of Sciences. https://doi.org/10.1073/pnas.90.20.9606
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