PGC-1: A Multifunctional Transcriptional Coactivator Involved in Human Metabolic Disorders

Authors: H. Oberkofler; F. Krempler; W. Patsch

Source: Current Genomics, Volume 5, Number 5, July 2004 , pp. 443-451(9)

Publisher: Bentham Science Publishers

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Abstract:

Nuclear hormone receptor function is controlled by a number of ancillary factors termed coregulators. Such coactivators and corepressors afford considerable flexibility in the coordinate expression of gene networks in numerous physiological, developmental and metabolic processes. PGC-1 agr

, originally described as transcriptional coactivator of PPAR ggr

, has since been shown to act in a much broader context. PGC-1 agr

coordinates the transcriptional programs of several key cellular pathways including mitochondrial biogenesis, thermogenesis, hepatic gluconeogenesis and bgr

- oxidation of fatty acids via interactions with a growing number of transcription factors. A central issue to understand the diverse functions of PGC-1 agr

is to gain insight into the mechanisms that confer specificity to its interactions with transfactors in response to intra- and extracellular signals. This review focuses on the different modes of regulation of PGC-1 agr

function and the implications for tissue and context-specific transcriptional responses. Moreover, the role of sequence substitutions at the PGC-1 agr