CCAAT/enhancer binding protein alpha uses distinct domains to prolong pituitary cells in the growth 1 and DNA synthesis phases of the cell cycle.

Weiqun Liu, John F. Enwright, William Hyun, Richard N. Day, Fred Schaufele

Research output: Contribution to journalArticle

Abstract

BACKGROUND: A number of transcription factors coordinate differentiation by simultaneously regulating gene expression and cell proliferation. CCAAT/enhancer binding protein alpha (C/EBPalpha) is a basic/leucine zipper transcription factor that integrates transcription with proliferation to regulate the differentiation of tissues involved in energy balance. In the pituitary, C/EBPalpha regulates the transcription of a key metabolic regulator, growth hormone. RESULTS: We examined the consequences of C/EBPalpha expression on proliferation of the transformed, mouse GHFT1-5 pituitary progenitor cell line. In contrast to mature pituitary cells, GHFT1-5 cells do not contain C/EBPalpha. Ectopic expression of C/EBPalpha in the progenitor cells resulted in prolongation of both growth 1 (G1) and the DNA synthesis (S) phases of the cell cycle. Transcription activation domain 1 and 2 of C/EBPalpha were required for prolongation of G1, but not of S. Some transcriptionally inactive derivatives of C/EBPalpha remained competent for G1 and S phase prolongation. C/EBPalpha deleted of its leucine zipper dimerization functions was as effective as full-length C/EBPalpha in prolonging G1 and S. CONCLUSION: We found that C/EBPalpha utilizes mechanistically distinct activities to prolong the cell cycle in G1 and S in pituitary progenitor cells. G1 and S phase prolongation did not require that C/EBPalpha remained transcriptionally active or retained the ability to dimerize via the leucine zipper. G1, but not S, arrest required a domain overlapping with C/EBPalpha transcription activation functions 1 and 2. Separation of mechanisms governing proliferation and transcription permits C/EBPalpha to regulate gene expression independently of its effects on proliferation.

Original languageEnglish (US)
Pages (from-to)6
Number of pages1
JournalBMC cell biology [electronic resource]
Volume3
Issue number1
StatePublished - Mar 21 2002
Externally publishedYes

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CCAAT-Enhancer-Binding Protein-alpha
Cell Cycle
DNA
Growth
S Phase
Leucine Zippers
Stem Cells
Transcriptional Activation
Basic-Leucine Zipper Transcription Factors
Gene Expression
Dimerization

ASJC Scopus subject areas

  • Cell Biology

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CCAAT/enhancer binding protein alpha uses distinct domains to prolong pituitary cells in the growth 1 and DNA synthesis phases of the cell cycle. / Liu, Weiqun; Enwright, John F.; Hyun, William; Day, Richard N.; Schaufele, Fred.

In: BMC cell biology [electronic resource], Vol. 3, No. 1, 21.03.2002, p. 6.

Research output: Contribution to journalArticle

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