title: ARTS and Siah collaborate in a pathway for XIAP degradation.
abstract: ARTS (apoptosis-related protein in the TGF-β signaling pathway) is a mitochondrial protein that binds XIAP (X-linked inhibitor of apoptosis protein) upon entering the cytosol, thus promoting cell death. Expression of ARTS is lost in some malignancies. Here, we show that ARTS binds to XIAP at BIR1, a domain distinct from the caspase-binding sites. Furthermore, ARTS interacts with the E3 ligase Siah-1 (seven in absentia homolog 1) to induce ubiquitination and degradation of XIAP. Cells lacking either Siah or ARTS contain higher steady-state levels of XIAP. Thus, ARTS serves as an adaptor to bridge Siah-1 to XIAP, targeting it for destruction.
authors.affiliation: Sanford-Burnham Medical Research Institute, La Jolla, CA 92037, USA.
authors.forename: Jason B
authors.initials: JB
authors.lastname: Garrison
authors.forename: Ricardo G
authors.initials: RG
authors.lastname: Correa
authors.forename: Motti
authors.initials: M
authors.lastname: Gerlic
authors.forename: Kenneth W
authors.initials: KW
authors.lastname: Yip
authors.forename: Andreas
authors.initials: A
authors.lastname: Krieg
authors.forename: Craig M
authors.initials: CM
authors.lastname: Tamble
authors.forename: Ranxin
authors.initials: R
authors.lastname: Shi
authors.forename: Kate
authors.initials: K
authors.lastname: Welsh
authors.forename: Srinivas
authors.initials: S
authors.lastname: Duggineni
authors.forename: Ziwei
authors.initials: Z
authors.lastname: Huang
authors.forename: Keqin
authors.initials: K
authors.lastname: Ren
authors.forename: Chunying
authors.initials: C
authors.lastname: Du
authors.forename: John C
authors.initials: JC
authors.lastname: Reed
mesh_terms: D000818:Animals; D017209:Apoptosis; D001665:Binding Sites; D002460:Cell Line; D057809:HEK293 Cells; D006801:Humans; D051379:Mice; D009687:Nuclear Proteins / Q000378:metabolism / Q000502:physiology*; D025941:Protein Interaction Mapping; D058112:Septins / Q000378:metabolism / Q000502:physiology*; D044767:Ubiquitin-Protein Ligases / Q000378:metabolism / Q000502:physiology*; D054875:Ubiquitination; D051636:X-Linked Inhibitor of Apoptosis Protein / Q000378:metabolism*; D000098563:Seven in Absentia Proteins
chemical_list: D009687:Nuclear Proteins; D051636:X-Linked Inhibitor of Apoptosis Protein; C496866:XIAP protein, human; D044767:Ubiquitin-Protein Ligases; D000098563:Seven in Absentia Proteins; C492027:SEPTIN4 protein, human; D058112:Septins