Mitotic clonal expansion: A synchronous process required for adipogenesis

Qi Qun Tang, Tamara C. Otto, M. Daniel Lane

Research output: Contribution to journalArticlepeer-review

Abstract

When induced to differentiate, growth-arrested 3T3-L1 preadipocytes synchronously reenter the cell cycle and undergo mitotic clonal expansion (MCE) followed by expression of genes that produce the adipocyte phenotype. The preadipocytes traverse the G1/S checkpoint synchronously as evidenced by the expression/activation of cdk2-cyclin-E/A, turnover of p27/kip1, hyperphosphorylation of Rb, translocation of cyclin D1 from nuclei to cytoplasm and GSK-3β from cytoplasm to nuclei, and incorporation of [3H]thymidine into DNA. As the cells cross the G1/S checkpoint, C/EBPβ acquires DNA-binding activity, initiating a cascade of transcriptional activation that culminates in the expression of adipocyte proteins. The mitogen-activated protein kinase/extracellular signal-regulated kinase kinase (MEK) inhibitor PD98059 delays, but does not block, MCE and differentiation, the extent of the delay causing a comparable delay in the expression of cell-cycle markers, MCE, and adipogenesis. The more potent and specific MEK inhibitor UO126 and the cyclin-dependent kinase inhibitor roscovitine, which inhibit the cell cycle at different points, block MCE, expression of cell cycle and adipocyte markers, as well as adipogenesis. These results show that MCE is a prerequisite for differentiation of 3T3-L1 preadipocytes into adipocytes.

Original languageEnglish (US)
Pages (from-to)44-49
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume100
Issue number1
DOIs
StatePublished - Jan 7 2003
Externally publishedYes

Keywords

  • 3T3-L1
  • Adipogenesis
  • C/EBPα
  • Cell cycle
  • PPARγ
  • Preadipocyte

ASJC Scopus subject areas

  • Genetics
  • General

Fingerprint Dive into the research topics of 'Mitotic clonal expansion: A synchronous process required for adipogenesis'. Together they form a unique fingerprint.

Cite this