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 Day, Fred Schaufele

Research output: Contribution to journalArticle

7 Citations (Scopus)

Abstract

Background: A number of transcription factors coordinate differentiation by simultaneously regulating gene expression and cell proliferation. CCAAT/enhancer binding protein alpha (C/EBPα) 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/EBPa regulates the transcription of a key metabolic regulator, growth hormone. Results: We examined the consequences of C/EBPα 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/EBPα. Ectopic expression of C/EBPα 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/EBPα were required for prolongation of G1, but not of S. Some transcriptionally inactive derivatives of C/EBPα remained competent for G1 and S phase prolongation. C/EBPα deleted of its leucine zipper dimerization functions was as effective as fulllength C/EBPα in prolonging G1 and S. Conclusion: We found that C/EBPα 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/ EBPα remained transcriptionally active or retained the ability to dimerize via the leucine zipper. G1, but not S, arrest required a domain overlapping with C/EBPα transcription activation functions 1 and 2. Separation of mechanisms governing proliferation and transcription permits C/EBPα to regulate gene expression independently of its effects on proliferation.

Original languageEnglish (US)
Article number6
JournalBMC cell biology [electronic resource]
Volume3
DOIs
StatePublished - Jan 4 2002
Externally publishedYes

Fingerprint

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
Growth Hormone

ASJC Scopus subject areas

  • Cell Biology

Cite this

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; Schaufele, Fred.

In: BMC cell biology [electronic resource], Vol. 3, 6, 04.01.2002.

Research output: Contribution to journalArticle

@article{31cc2969f31742b294b8be932a0cf71b,
title = "CCAAT/enhancer binding protein alpha uses distinct domains to prolong pituitary cells in the growth 1 and DNA synthesis phases of the cell cycle",
abstract = "Background: A number of transcription factors coordinate differentiation by simultaneously regulating gene expression and cell proliferation. CCAAT/enhancer binding protein alpha (C/EBPα) 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/EBPa regulates the transcription of a key metabolic regulator, growth hormone. Results: We examined the consequences of C/EBPα 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/EBPα. Ectopic expression of C/EBPα 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/EBPα were required for prolongation of G1, but not of S. Some transcriptionally inactive derivatives of C/EBPα remained competent for G1 and S phase prolongation. C/EBPα deleted of its leucine zipper dimerization functions was as effective as fulllength C/EBPα in prolonging G1 and S. Conclusion: We found that C/EBPα 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/ EBPα remained transcriptionally active or retained the ability to dimerize via the leucine zipper. G1, but not S, arrest required a domain overlapping with C/EBPα transcription activation functions 1 and 2. Separation of mechanisms governing proliferation and transcription permits C/EBPα to regulate gene expression independently of its effects on proliferation.",
author = "Weiqun Liu and Enwright, {John F.} and William Hyun and Richard Day and Fred Schaufele",
year = "2002",
month = "1",
day = "4",
doi = "10.1186/1471-2121-3-6",
language = "English (US)",
volume = "3",
journal = "BMC Cell Biology",
issn = "1471-2121",
publisher = "BioMed Central",

}

TY - JOUR

T1 - CCAAT/enhancer binding protein alpha uses distinct domains to prolong pituitary cells in the growth 1 and DNA synthesis phases of the cell cycle

AU - Liu, Weiqun

AU - Enwright, John F.

AU - Hyun, William

AU - Day, Richard

AU - Schaufele, Fred

PY - 2002/1/4

Y1 - 2002/1/4

N2 - Background: A number of transcription factors coordinate differentiation by simultaneously regulating gene expression and cell proliferation. CCAAT/enhancer binding protein alpha (C/EBPα) 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/EBPa regulates the transcription of a key metabolic regulator, growth hormone. Results: We examined the consequences of C/EBPα 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/EBPα. Ectopic expression of C/EBPα 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/EBPα were required for prolongation of G1, but not of S. Some transcriptionally inactive derivatives of C/EBPα remained competent for G1 and S phase prolongation. C/EBPα deleted of its leucine zipper dimerization functions was as effective as fulllength C/EBPα in prolonging G1 and S. Conclusion: We found that C/EBPα 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/ EBPα remained transcriptionally active or retained the ability to dimerize via the leucine zipper. G1, but not S, arrest required a domain overlapping with C/EBPα transcription activation functions 1 and 2. Separation of mechanisms governing proliferation and transcription permits C/EBPα to regulate gene expression independently of its effects on proliferation.

AB - Background: A number of transcription factors coordinate differentiation by simultaneously regulating gene expression and cell proliferation. CCAAT/enhancer binding protein alpha (C/EBPα) 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/EBPa regulates the transcription of a key metabolic regulator, growth hormone. Results: We examined the consequences of C/EBPα 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/EBPα. Ectopic expression of C/EBPα 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/EBPα were required for prolongation of G1, but not of S. Some transcriptionally inactive derivatives of C/EBPα remained competent for G1 and S phase prolongation. C/EBPα deleted of its leucine zipper dimerization functions was as effective as fulllength C/EBPα in prolonging G1 and S. Conclusion: We found that C/EBPα 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/ EBPα remained transcriptionally active or retained the ability to dimerize via the leucine zipper. G1, but not S, arrest required a domain overlapping with C/EBPα transcription activation functions 1 and 2. Separation of mechanisms governing proliferation and transcription permits C/EBPα to regulate gene expression independently of its effects on proliferation.

UR - http://www.scopus.com/inward/record.url?scp=2342555616&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=2342555616&partnerID=8YFLogxK

U2 - 10.1186/1471-2121-3-6

DO - 10.1186/1471-2121-3-6

M3 - Article

VL - 3

JO - BMC Cell Biology

JF - BMC Cell Biology

SN - 1471-2121

M1 - 6

ER -