The opposite role of two UBA–UBX containing proteins, p47 and SAKS1 in the degradation of a single ERAD substrate, α-TCR

详细信息    查看全文

• 作者：Eun Sil Park ; Yung Joon Yoo ; Muthukumar Elangovan
• 关键词：α ; TCR ; α1 ; antitrypsin ; δCD3 ; ERAD ; ER stress ; Proteosomal degradation ; UBA–UBX protein ; Ubiquitin
• 刊名：Molecular and Cellular Biochemistry
• 出版年：2017
• 出版时间：January 2017
• 年：2017
• 卷：425
• 期：1-2
• 页码：37-45
• 全文大小：
• 刊物类别：Biomedical and Life Sciences
• 刊物主题：Biochemistry, general; Medical Biochemistry; Oncology; Cardiology;
• 出版者：Springer US
• ISSN：1573-4919
• 卷排序：425

文摘

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.