Characterization of the transactivation domain in the peroxisome- proliferator-activated receptor γ co-activator (PGC-1)

Prabodh Sadana, Edwards Park

Research output: Contribution to journalArticle

13 Citations (Scopus)

Abstract

The PGC-1s (peroxisome-proliferator-activated receptor γ coactivators) are a family of transcriptional regulators that induce the expression of various metabolic genes. PGC-1 proteins stimulate genes involved in mitochondrial biogenesis, fatty acid oxidation and hepatic gluconeogenesis. Previous studies have demonstrated that the PGC-1α and β isoforms interact with nuclear receptors through the conserved LXXLL (leucine-X-X- leucine-leucine) motifs. In the present study, we have investigated the mechanisms by which these PGC-1 isoforms stimulate gene expression. We have determined that the N-terminus of PGC-1 is responsible for transcriptional activation. Two conserved peptide motifs were identified in the N-terminus of PGC-1α and β isoforms. These domains were named AD1 and AD2 (activation domain 1 and 2). Deletion of both of these motifs decreased the induction of various PGC-1-regulated genes including the PEPCK (phosphoenolpyruvate carboxykinase) and CPT-I (carnitine palmitoyltransferase-I) genes. It was determined that amino acids containing a negative charge in AD1 and the leucine residues in AD2 were important for the transcriptional induction of the PEPCK and CPT-I genes. Disruption of the AD motifs did not diminish the ability of the PGC-1α protein to associate with the PEPCK or CPT-I genes. In addition, deletion of the AD domains did not eliminate the ability of PGC-1α to interact with the thyroid hormone receptor. The data indicate that the AD1 and AD2 motifs mediate the induction of many PGC-1-responsive genes, but they do not contribute to the recruitment of PGC-1 to target genes.

Original languageEnglish (US)
Pages (from-to)511-518
Number of pages8
JournalBiochemical Journal
Volume403
Issue number3
DOIs
StatePublished - May 1 2007

Fingerprint

Peroxisome Proliferator-Activated Receptors
Transcriptional Activation
Genes
Carnitine O-Palmitoyltransferase
Leucine
Phosphoenolpyruvate
Chemical activation
Protein Isoforms
Thyroid Hormone Receptors
Gluconeogenesis
Organelle Biogenesis
Cytoplasmic and Nuclear Receptors
Gene expression
Proteins
Fatty Acids
Gene Expression
Amino Acids
Oxidation
Peptides
Liver

All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Molecular Biology
  • Cell Biology

Cite this

Characterization of the transactivation domain in the peroxisome- proliferator-activated receptor γ co-activator (PGC-1). / Sadana, Prabodh; Park, Edwards.

In: Biochemical Journal, Vol. 403, No. 3, 01.05.2007, p. 511-518.

Research output: Contribution to journalArticle

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