title: Dimerization of hSiah proteins regulates their stability.
abstract: HSiah1 and 2 are members of the Ring finger-type family of ubiquitin E3-ligase proteins. They contribute to the degradation of multiple targets by interacting with both the ubiquitin conjugating enzyme E2 and the substrate to be ubiquitylated prior to proteasomal degradation. Ring finger proteins have also been shown to regulate their own stability through the proteasomal degradation. Here, we report that hSiah2 proteins can form not only homodimers but also heterodimers with hSiah1 independently from their Ring finger domain. The oligomerization process, in turn, mediates a Ring finger-dependent proteasomal degradation of the two proteins. In contrast, such a catalytic activity is not observed for hSiah1. Therefore, these results show that the two isoforms exhibit differential regulatory properties. Additionally, dimerization provides a mechanism to control the steady-state levels of these two enzymes responsible for important catalytic activities.
authors.affiliation: Institut Cochin, U567 Inserm, UMR CNRS 8104, Université Paris V, Dpt d'Hématologie, 27 rue du Fg St Jacques, 75014 Paris, France.
authors.forename: Arnaud
authors.initials: A
authors.lastname: Depaux
authors.forename: Fabienne
authors.initials: F
authors.lastname: Regnier-Ricard
authors.forename: Antonia
authors.initials: A
authors.lastname: Germani
authors.forename: Nadine
authors.initials: N
authors.lastname: Varin-Blank
mesh_terms: D020816:Amino Acid Motifs; D020134:Catalytic Domain; D002460:Cell Line; D019281:Dimerization; D004795:Enzyme Stability; D006801:Humans; D007527:Isoenzymes / Q000737:chemistry / Q000378:metabolism; D009687:Nuclear Proteins / Q000737:chemistry* / Q000378:metabolism*; D017434:Protein Structure, Tertiary; D040681:Structural Homology, Protein; D044767:Ubiquitin-Protein Ligases / Q000737:chemistry* / Q000378:metabolism*; D000098563:Seven in Absentia Proteins
chemical_list: D007527:Isoenzymes; D009687:Nuclear Proteins; D044767:Ubiquitin-Protein Ligases; D000098563:Seven in Absentia Proteins