Unique proteasome subunit Xrpn10c is a specific receptor for the antiapoptotic ubiquitin-like protein Scythe.
The Rpn10 subunit of the 26S proteasome can bind to polyubiquitinoylated and/or ubiquitin-like proteins via ubiquitin-interacting motifs (UIMs). Vertebrate Rpn10 consists of five distinct spliced isoforms, but the specific functions of these variants remain largely unknown. We report here that one of the alternative products of Xenopus Rpn10, named Xrpn10c, functions as a specific receptor for Scythe/BAG-6, which has been reported to regulate Reaper-induced apoptosis. Deletional analyses revealed that Scythe has at least two distinct domains responsible for its binding to Xrpn10c. Conversely, an Xrpn10c has a UIM-independent Scythe-binding site. The forced expression of a Scythe mutant protein lacking Xrpn10c-binding domains in Xenopus embryos induces inappropriate embryonic death, whereas the wild-type Scythe did not show any abnormality. The results indicate that Xrpn10c-binding sites of Scythe act as an essential segment linking the ubiquitin/proteasome machinery to the control of proper embryonic development.
Kikukawa
Yuhsuke
Y
Department of Biochemistry, Graduate School of Pharmaceutical Sciences, Hokkaido University, Sapporo, Japan.
Minami
Ryosuke
R
Shimada
Masumi
M
Kobayashi
Masami
M
Tanaka
Keiji
K
Yokosawa
Hideyoshi
H
Kawahara
Hiroyuki
H
D000818:Animals; D017209:Apoptosis; D001483:Base Sequence; D001665:Binding Sites; D002352:Carrier Proteins / Q000235:genetics / Q000502:physiology*; D004625:Embryo, Nonmammalian; D047108:Embryonic Development; D018832:Molecular Chaperones; D008969:Molecular Sequence Data; D046988:Proteasome Endopeptidase Complex / Q000502:physiology*; D021122:Protein Subunits; D029867:Xenopus Proteins / Q000235:genetics / Q000502:physiology*
C116358:BAG6 protein, Xenopus; D002352:Carrier Proteins; D018832:Molecular Chaperones; D021122:Protein Subunits; C507395:Rpn10c protein, Xenopus; D029867:Xenopus Proteins; D046988:Proteasome Endopeptidase Complex; C061553:ATP dependent 26S protease