Functional differences between two major ubiquitin receptors in the proteasome; S5a and hRpn13.
It is well known that S5a and hRpn13 are two major ubiquitin (Ub) receptors in the proteasome but little is known about their functional difference in recruiting ubiquitinated substrates. In this study using siRNA-mediated knockdown of S5a or hRpn13, we found that two Ub receptors had different substrate specificity although similar level of accumulation of high molecular weight Ub-conjugates was observed. Interesting enough, depletion of S5a, but not hRpn13, resulted in the Ub-containing aggregates and induced ER chaperones such as Grp78 and Grp94. ERAD substrates such as alpha-TCR and alpha1-antitrypsin were also stabilized by the depletion of S5a but not hRpn13. Our results suggest that there is different substrate specificity between S5a and hRpn13 at the level of delivery and S5a may be the major docking site for ERAD substrates.
Elangovan
Muthukumar
M
School of Life Sciences, Gwangju Institute of Science & Technology, 1 Oryong-dong Buk-ku, Gwangju 500-712, Republic of Korea.
Oh
Choongseob
C
Sukumaran
Lavanya
L
Wójcik
Cezary
C
Yoo
Yung Joon
YJ
D004721:Endoplasmic Reticulum / Q000378:metabolism; D000091342:Endoplasmic Reticulum Chaperone BiP; D055785:Gene Knockdown Techniques; D018840:HSP70 Heat-Shock Proteins / Q000378:metabolism; D006367:HeLa Cells; D006360:Heat-Shock Proteins / Q000378:metabolism; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins; D008562:Membrane Glycoproteins / Q000235:genetics / Q000378:metabolism*; D008565:Membrane Proteins / Q000378:metabolism; D018832:Molecular Chaperones / Q000378:metabolism; D046988:Proteasome Endopeptidase Complex / Q000235:genetics / Q000378:metabolism*; D055550:Protein Stability; D034741:RNA, Small Interfering / Q000235:genetics; D016601:RNA-Binding Proteins; D013379:Substrate Specificity; D025801:Ubiquitin / Q000378:metabolism*
C500781:ADRM1 protein, human; D000091342:Endoplasmic Reticulum Chaperone BiP; D018840:HSP70 Heat-Shock Proteins; C000717247:HSPA5 protein, human; D006360:Heat-Shock Proteins; D047908:Intracellular Signaling Peptides and Proteins; D008562:Membrane Glycoproteins; D008565:Membrane Proteins; D018832:Molecular Chaperones; C498506:PSMD4 protein, human; D034741:RNA, Small Interfering; D016601:RNA-Binding Proteins; D025801:Ubiquitin; C018551:glucose-regulated proteins; D046988:Proteasome Endopeptidase Complex