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In the present study we show that dysfunctional Pex7p, including mutants from RCDP patients, is degraded by a ubiquitin-dependent proteasomal pathway involving the CRL4A (Cullin4A-RING ubiquitin ligase) complex. Furthermore, we demonstrate that the degradation of dysfunctional Pex7p is essential for maintaining normal PTS2 import, thereby suggesting that CRL4A functions as an E3 ligase in the quality control of Pex7p. Our results define a mechanism underlying Pex7p homoeostasis and highlight its importance for regulating PTS2 import. These findings may lead to a new approach to Pex7p-based therapies for the treatment of peroxisome biogenesis disorders such as RCDP.<\/jats:p>","DOI":"10.1042\/bj20130861","type":"journal-article","created":{"date-parts":[[2014,7,16]],"date-time":"2014-07-16T12:35:50Z","timestamp":1405514150000},"page":"65-74","update-policy":"https:\/\/doi.org\/10.1042\/crossmark_policy","source":"Crossref","is-referenced-by-count":14,"title":["CUL4A-DDB1-Rbx1 E3 ligase controls the quality of the PTS2 receptor Pex7p"],"prefix":"10.1042","volume":"463","author":[{"given":"Yasuhiro","family":"Miyauchi-Nanri","sequence":"first","affiliation":[{"name":"Department of Biology, Faculty of Sciences, Kyushu University, Fukuoka 812-8581, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Satoru","family":"Mukai","sequence":"additional","affiliation":[{"name":"Department of Biology, Faculty of Sciences, Kyushu University, Fukuoka 812-8581, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kosuke","family":"Kuroda","sequence":"additional","affiliation":[{"name":"Graduate School of Systems Life Sciences, Kyushu University, Fukuoka 812-8581, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yukio","family":"Fujiki","sequence":"additional","affiliation":[{"name":"Department of Biology, Faculty of Sciences, Kyushu University, Fukuoka 812-8581, Japan"},{"name":"Graduate School of Systems Life Sciences, Kyushu University, Fukuoka 812-8581, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"288","published-online":{"date-parts":[[2014,9,8]]},"reference":[{"key":"2021112216073459200_B1","doi-asserted-by":"publisher","first-page":"157","DOI":"10.1146\/annurev.bi.61.070192.001105","article-title":"Biochemistry of peroxisomes","volume":"61","author":"van den Bosch","year":"1992","journal-title":"Annu. 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