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The ubiquitin\u2010proteasome 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\u2010chaperone with E3 activity, plays a pivotal role in determining the fates of the damaged proteins. The delicate balance between UPP\u2010mediated 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.<\/jats:p>","DOI":"10.1096\/fj.05-5080fje","type":"journal-article","created":{"date-parts":[[2006,2,9]],"date-time":"2006-02-09T20:34:20Z","timestamp":1139517260000},"page":"741-743","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":93,"title":["The triage of damaged proteins: degradation by the ubiquitin\u2010proteasome pathway or repair by molecular chaperones"],"prefix":"10.1096","volume":"20","author":[{"given":"Carla","family":"Marques","sequence":"first","affiliation":[{"name":"Human Nutrition Research Center on Aging Tufts University  Boston Massachusetts"},{"name":"Center of Ophthalmology IBILI Faculty of Medicine University of Coimbra  Portugal"}]},{"given":"Weimin","family":"Guo","sequence":"additional","affiliation":[{"name":"Human Nutrition Research Center on Aging Tufts University  Boston Massachusetts"}]},{"given":"Paulo","family":"Pereira","sequence":"additional","affiliation":[{"name":"Center of Ophthalmology IBILI Faculty of Medicine University of Coimbra  Portugal"}]},{"given":"Allen","family":"Taylor","sequence":"additional","affiliation":[{"name":"Human Nutrition Research Center on Aging Tufts University  Boston Massachusetts"}]},{"given":"Cam","family":"Patterson","sequence":"additional","affiliation":[{"name":"Carolina Cardiovascular Biology Center University of North Carolina  Chapel Hill North Carolina"}]},{"given":"Paul C.","family":"Evans","sequence":"additional","affiliation":[{"name":"BHF Cardiovascular Medicine Imperial College  London United Kingdom"}]},{"given":"Fu","family":"Shang","sequence":"additional","affiliation":[{"name":"Human Nutrition Research Center on Aging Tufts University  Boston Massachusetts"}]}],"member":"311","published-online":{"date-parts":[[2006,2,9]]},"reference":[{"key":"e_1_2_6_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0962-8924(00)01852-3"},{"key":"e_1_2_6_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0092-8674(01)00244-6"},{"key":"e_1_2_6_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.tcb.2004.10.006"},{"key":"e_1_2_6_5_1","doi-asserted-by":"publisher","DOI":"10.1038\/35008096"},{"key":"e_1_2_6_6_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1237797100"},{"key":"e_1_2_6_7_1","doi-asserted-by":"publisher","DOI":"10.1152\/physrev.00027.2001"},{"key":"e_1_2_6_8_1","doi-asserted-by":"publisher","DOI":"10.1093\/jn\/129.11.1933"},{"key":"e_1_2_6_9_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrm1492"},{"key":"e_1_2_6_10_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M000434200"},{"key":"e_1_2_6_11_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M002035200"},{"key":"e_1_2_6_12_1","doi-asserted-by":"publisher","DOI":"10.1093\/emboj\/17.23.6879"},{"key":"e_1_2_6_13_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.271.32.19617"},{"key":"e_1_2_6_14_1","doi-asserted-by":"publisher","DOI":"10.1023\/A:1022455621111"},{"key":"e_1_2_6_15_1","doi-asserted-by":"publisher","DOI":"10.1515\/bchm.1998.379.10.1217"},{"key":"e_1_2_6_16_1","doi-asserted-by":"publisher","DOI":"10.1128\/MCB.19.6.4535"},{"key":"e_1_2_6_17_1","doi-asserted-by":"publisher","DOI":"10.1038\/35055162"},{"key":"e_1_2_6_18_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0968-0004(02)02125-4"},{"key":"e_1_2_6_19_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.286.5446.1888"},{"key":"e_1_2_6_20_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature02263"},{"key":"e_1_2_6_21_1","doi-asserted-by":"publisher","DOI":"10.1128\/MCB.18.1.30"},{"key":"e_1_2_6_22_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.272.14.9002"},{"key":"e_1_2_6_23_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M209682200"},{"key":"e_1_2_6_24_1","doi-asserted-by":"publisher","DOI":"10.1038\/35050618"},{"key":"e_1_2_6_25_1","doi-asserted-by":"crossref","first-page":"13760","DOI":"10.1016\/S0021-9258(18)67085-1","article-title":"The eye lens has an active ubiquitin\u2010protein conjugation system","volume":"261","author":"Jahngen J. 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