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AEBP1: A signaling modulator of MAPK activation for adipogenesis.

Date

2000

Authors

Kim, Sungwoo.

Journal Title

Journal ISSN

Volume Title

Publisher

Dalhousie University

Abstract

Description

The activation of mitogen-activated protein kinase (MAPK) is a vital step in signaling cascades which regulate cell growth and cell differentiation. MAP kinase activation is a reversible process in which protein phosphatases play a crucial role in controlling cellular activities. Thus, the regulation of prolonged or transient MAP kinase activation may be through phosphatases rather than through the activity of MEK which is itself transiently activated by phosphorylation. In adipogenesis, a complex process in which multiple hormones and factors regulate the conversion of progenitor cells into adipocytes, MAPK activation inhibits the differentiation process. The regulatory mechanisms or the cellular factors that regulate the switch from growth to differentiation in the adipogenic lineage are largely unelucidated. Furthermore, AEBP1, a transcription factor that is down-regulated during adipogenesis, is now known to interact with MAPK.
In this thesis, I show that AEBP1 complexes with MAPK through its N-terminal domain. This interaction protects MAPK activity from dephosphorylation by its specific phosphatase and sustains MAPK activation. AEBP1 levels decrease during adipocyte differentiation in 3T3-L1 cells and as a result of this the associated MAPK decreases. Overexpression of AEBP1 blocks the adipocyte differentiation by enhancing MAP kinase activity whereas the inhibition of protective activity of endogenous AEBP1 stimulates the adipocyte differentiation. These results suggest that enhancement of MAPK activation by the protective effect of AEBP1 may constitute a critical part in the determination of either cell growth or differentiation in the adipogenic lineage. The proposed mode of action by which a transcription factor regulates MAPK activation is novel.
Thesis (Ph.D.)--Dalhousie University (Canada), 2000.

Keywords

Biology, Molecular.

Citation