title: The opposite role of two UBA-UBX containing proteins, p47 and SAKS1 in the degradation of a single ERAD substrate, α-TCR.
abstract: The UBA-UBX domain-containing proteins can interact with ubiquitinated substrates and p97 during endoplasmic reticulum-associated degradation (ERAD). Here, we found that the expressions of all UBA-UBX genes p47, SAKS1, UBXD8, FAF1, and UBXD7 were elevated upon ER stress, albeit with different levels. Of which p47, SAKS1, and UBXD8 are 'immediate' respondents whereas FAF1 and UBXD7 were 'late' respondents to ER stress. Interestingly, the expression of specific UBA-UBX genes were altered in cells stably expressing three different ERAD substrates such as α-TCR, α1-antitrypsin, and δCD3. We first found that p47 and UBXD8 expression levels were increased in α-TCR and α1-antitrypsin stable cell lines, respectively, whereas SAKS1 expression level was reduced in all the three ERAD substrates tested. Of note, we also found p47 promotes, whereas SASK1 delays the degradation of a single ERAD substrate, α-TCR. Additionally, we found that SAKS1 selectively inhibits the degradation of ERAD substrates without affecting cytosolic proteasomal substrates. Taken together, our results identified that UBA-UBX proteins possess substrate selectivity and opposite role of two different UBA-UBX proteins in the degradation of a single ERAD substrate.
authors: School of Life Sciences, Gwangju Institute of Science & Technology (GIST), 123 Cheomdangwagi-ro, Buk-gu, Gwangju, 61005, Republic of Korea.
authors: Eun Sil
authors: ES
authors: Park
authors: School of Life Sciences, Gwangju Institute of Science & Technology (GIST), 123 Cheomdangwagi-ro, Buk-gu, Gwangju, 61005, Republic of Korea.
authors: Yung Joon
authors: YJ
authors: Yoo
authors: School of Life Sciences, Gwangju Institute of Science & Technology (GIST), 123 Cheomdangwagi-ro, Buk-gu, Gwangju, 61005, Republic of Korea. muthu@gist.ac.kr.
authors: Muthukumar
authors: http://orcid.org/0000-0002-7590-3584
authors: M
authors: Elangovan
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics / Q000378:metabolism*; D001798:Blood Proteins / Q000235:genetics / Q000378:metabolism; D060746:Endoplasmic Reticulum-Associated Degradation / Q000502:physiology*; D006367:HeLa Cells; D006801:Humans; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism; D059748:Proteolysis; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000235:genetics / Q000378:metabolism*
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D001798:Blood Proteins; C468782:FAF2 protein, human; D008565:Membrane Proteins; D016693:Receptors, Antigen, T-Cell, alpha-beta; C504037:UBXN1 protein, human; C553975:p37 protein, human
keywords: ER stress; ERAD; Proteosomal degradation; UBA–UBX protein; Ubiquitin; α-TCR; α1-antitrypsin; δCD3