title: HECT ubiquitin ligase Smurf1 targets the tumor suppressor ING2 for ubiquitination and degradation.
abstract: Inhibitor of growth 2 (ING2) gene encodes a candidate tumor suppressor and is frequently reduced in many tumors. However, the mechanisms underlying the regulation of ING2, in particular its protein stability, are still unclear. Here we show that the homologous to E6AP carboxyl terminus (HECT)-type ubiquitin ligase Smad ubiquitination regulatory factor 1 (Smurf1) interacts with and targets ING2 for poly-ubiquitination and proteasomal degradation. Intriguingly, the ING2 binding domain in Smurf1 was mapped to the catalytic HECT domain. Furthermore, the C-terminal PHD domain of ING2 was required for Smurf1-mediated degradation. This study provided the first evidence that the stability of ING2 could be regulated by ubiquitin-mediated degradation.
authors.affiliation: Department of Biology Sciences and Biotechnology, Tsinghua University, Beijing, China.
authors.forename: Jing
authors.initials: J
authors.lastname: Nie
authors.forename: Lin
authors.initials: L
authors.lastname: Liu
authors.forename: Min
authors.initials: M
authors.lastname: Wu
authors.forename: Guichun
authors.initials: G
authors.lastname: Xing
authors.forename: Shan
authors.initials: S
authors.lastname: He
authors.forename: Yuxin
authors.initials: Y
authors.lastname: Yin
authors.forename: Chunyan
authors.initials: C
authors.lastname: Tian
authors.forename: Fuchu
authors.initials: F
authors.lastname: He
authors.forename: Lingqiang
authors.initials: L
authors.lastname: Zhang
mesh_terms: D001669:Biochemical Phenomena; D016147:Genes, Tumor Suppressor; D006131:Growth Inhibitors / Q000235:genetics / Q000378:metabolism; D006801:Humans; D008025:Ligases / Q000235:genetics / Q000378:metabolism*; D046988:Proteasome Endopeptidase Complex / Q000235:genetics / Q000378:metabolism; D025801:Ubiquitin / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D054875:Ubiquitination
chemical_list: D006131:Growth Inhibitors; D025801:Ubiquitin; D046988:Proteasome Endopeptidase Complex; D008025:Ligases