title: Akt is negatively regulated by the MULAN E3 ligase.
abstract: The serine/threonine kinase Akt functions in multiple cellular processes, including cell survival and tumor development. Studies of the mechanisms that negatively regulate Akt have focused on dephosphorylation-mediated inactivation. In this study, we identified a negative regulator of Akt, MULAN, which possesses both a RING finger domain and E3 ubiquitin ligase activity. Akt was found to directly interact with MULAN and to be ubiquitinated by MULAN in vitro and in vivo. Other molecular assays demonstrated that phosphorylated Akt is a substantive target for both interaction with MULAN and ubiquitination by MULAN. The results of the functional studies suggest that the degradation of Akt by MULAN suppresses cell proliferation and viability. These data provide insight into the Akt ubiquitination signaling network.
authors.affiliation: Functional Genoproteome Research Centre, Konkuk University, Seoul 143-701, Korea.
authors.forename: Seunghee
authors.initials: S
authors.lastname: Bae
authors.forename: Sun-Yong
authors.initials: SY
authors.lastname: Kim
authors.forename: Jin Hyuk
authors.initials: JH
authors.lastname: Jung
authors.forename: Yeongmin
authors.initials: Y
authors.lastname: Yoon
authors.forename: Hwa Jun
authors.initials: HJ
authors.lastname: Cha
authors.forename: Hyunjin
authors.initials: H
authors.lastname: Lee
authors.forename: Karam
authors.initials: K
authors.lastname: Kim
authors.forename: Jongran
authors.initials: J
authors.lastname: Kim
authors.forename: In-Sook
authors.initials: IS
authors.lastname: An
authors.forename: Jongdoo
authors.initials: J
authors.lastname: Kim
authors.forename: Hong-Duck
authors.initials: HD
authors.lastname: Um
authors.forename: In-Chul
authors.initials: IC
authors.lastname: Park
authors.forename: Su-Jae
authors.initials: SJ
authors.lastname: Lee
authors.forename: Seon Young
authors.initials: SY
authors.lastname: Nam
authors.forename: Young-Woo
authors.initials: YW
authors.lastname: Jin
authors.forename: Jae Ho
authors.initials: JH
authors.lastname: Lee
authors.forename: Sungkwan
authors.initials: S
authors.lastname: An
mesh_terms: D049109:Cell Proliferation; D002470:Cell Survival; D057809:HEK293 Cells; D006367:HeLa Cells; D006801:Humans; D010766:Phosphorylation; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism*; D034622:RNA Interference; D034741:RNA, Small Interfering / Q000378:metabolism; D011993:Recombinant Fusion Proteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction; D044767:Ubiquitin-Protein Ligases / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D054875:Ubiquitination
chemical_list: D034741:RNA, Small Interfering; D011993:Recombinant Fusion Proteins; D044767:Ubiquitin-Protein Ligases; D051057:Proto-Oncogene Proteins c-akt