Format

Send to:

Choose Destination
See comment in PubMed Commons below
J Biol Chem. 2007 Aug 31;282(35):25970-80. Epub 2007 Jul 9.

Intramolecular control of protein stability, subnuclear compartmentalization, and coactivator function of peroxisome proliferator-activated receptor gamma coactivator 1alpha.

Author information

  • 1Department of Regenerative Medicine and Advanced Cardiac Therapeutics, Keio University School of Medicine, and Department of Rheumatology and Allergy, Research Hospital, Tokyo, Japan. msano@sc.itc.keio.ac.jp

Abstract

Peroxisome proliferator-activated receptor gamma coactivator (PGC)-1 is a critical transcriptional regulator of energy metabolism. Here we found that PGC-1alpha is a short lived and aggregation-prone protein. PGC-1alpha localized throughout the nucleoplasm and was rapidly destroyed via the ubiquitin-proteasome pathway. Upon proteasome inhibition, PGC-1alpha formed insoluble polyubiquitinated aggregates. Ubiquitination of PGC-1alpha depended on the integrity of the C terminus-containing arginine-serine-rich domains and an RNA recognition motif. Interestingly, ectopically expressed C-terminal fragment of PGC-1alpha was autonomously ubiquitinated and aggregated with promyelocytic leukemia protein. Cooperation of the N-terminal region containing two PEST-like motifs was required for prevention of aggregation and targeting of the polyubiquitinated PGC-1alpha for degradation. This region thereby negatively controlled the aggregation properties of the C-terminal region to regulate protein turnover and intranuclear compartmentalization of PGC-1alpha. Exogenous expression of the PGC-1alpha C-terminal fragment interfered with degradation of full-length PGC-1alpha and enhanced its coactivation properties. We concluded that PGC-1alpha function is critically regulated at multiple steps via intramolecular cooperation among several distinct structural domains of the protein.

PMID:
17620342
[PubMed - indexed for MEDLINE]
Free full text
PubMed Commons home

PubMed Commons

0 comments
How to join PubMed Commons

    Supplemental Content

    Full text links

    Icon for HighWire
    Loading ...
    Write to the Help Desk