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ARS Home » Northeast Area » Boston, Massachusetts » Jean Mayer Human Nutrition Research Center On Aging » Research » Publications at this Location » Publication #196139
Title: THE TRIAGE OF DAMAGED PROTEINS: DEGRADATION BY THE UBIQUITIN-PROTEASOME PATHWAY OR REPAIR BY MOLECULAR CHAPERONES

Author
item MARCQUES, CARLA - TUFTS/HNRCA
item GUO, WEIMIN - TUFTS/HNRCA
item PEREIRA, PAULO - UNIV OF COIMBRA, PORTUGAL
item Taylor, Allen
item PATTERSON, CAM - UNIV OF NORTH CAROLINA
item EVANS, PAUL - IMPERIAL COLLEGE, UK
item Shang, Fu

Submitted to: Federation of American Societies for Experimental Biology Conference
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 11/15/2005
Publication Date: 2/9/2006
Citation: Marcques, C., Guo, W., Pereira, P., Taylor, A., Patterson, C., Evans, P.C., Shang, F. 2006. The triage of damaged proteins: degradation by the ubiquitin-proteasome pathway or repair by molecular chaperones. Federation of American Societies for Experimental Biology Conference. 20(6):741-3.

Interpretive Summary: One of the causes that is directly related to age-related diseases is the accumulation of damaged proteins. The ubiquitin-proteasome pathway (UPP) is involved in selective degradatioin of damaged protein while molecular chaperones such as heat shock proteins are partially responsible for refolding denatured proteins. For the first time, this work demonstrates that the UPP and molecular chaperones work in a competitive manner, and that the results of denatured proteins are determined by the relative activities of the UPP and molecular chaperones. CHIP, a co-chaperone with E3 activity, has in important role in determining the outcome of the damaged proteins. The balance between UPP-mediated degradation and refolding of the denatured proteins is governed by certain levels of CHIP and other molecular chaperones. Isopeptidases, the enzymes that reverse the actions of CHIP, also play a significant part in determining the result of denatured proteins.

Technical Abstract: Accumulation of damaged proteins is causally related to many age-related diseases. The ubiquitin-proteasome pathway (UPP) plays a role in selective degradation of damaged proteins, whereas molecular chaperones, such as heat shock proteins, are involved in refolding denatured proteins. This work demonstrates for the first time that the UPP and molecular chaperones work in a competitive manner and that the fates of denatured proteins are determined by the relative activities of the UPP and molecular chaperones. Enhanced UPP activity suppresses the refolding of denatured proteins whereas elevated chaperone activity inhibits the degradation of denatured proteins. CHIP, a co-chaperone with E3 activity, plays a pivotal role in determining the fates of the damaged proteins. The delicate balance between UPP-mediated degradation and refolding of denatured proteins is governed by relative levels of CHIP and other molecular chaperones. Isopeptidases, the enzymes that reverse the actions of CHIP, also play an important role in determining the fate of denatured proteins.