A novel RCE1 isoform is required for H-Ras plasma membrane localization and is regulated by USP17

作者：Jaworski Jakub; Govender Ureshnie; McFarlane Cheryl; de la Vega Michelle; Greene Michelle K; Rawlings Neil D; Johnston James A; Scott Christopher J; Burrows James E^*

来源：Biochemical Journal, 2014, 457(2): 289-300.

DOI：10.1042/BJ20131213

• deubiquitination
• protease
• Ras
• Ras-converting enzyme 1 (RCE1)
• ubiquitin
• ubiquitin-specific protease 17 (USP17)

Processing of the %26apos;CaaX%26apos; motif found on the C-termini of many proteins, including the proto-oncogene Ras, requires the ER (endoplasmic reticulum)-resident protease RCE1 (Ras-converting enzyme 1) and is necessary for the proper localization and function of many of these %26apos;CaaX%26apos; proteins. In the present paper, we report that several mammalian species have a novel isoform (isoform 2) of RCE1 resulting from an alternate splice site and producing an N-terminally truncated protein. We demonstrate that both RCE1 isoform 1 and the newly identified isoform 2 are required to reinstate proper H-Ras processing and thus plasma membrane localization in RCE1-null cells. In addition, we show that the deubiquitinating enzyme USP17 (ubiquitin-specific protease 17), previously shown to modulate RCE1 activity, can regulate the abundance and localization of isoform 2. Furthermore, we show that isoform 2 is ubiquitinated on Lys(43) and deubiquitinated by USP17. Collectively, the findings of the present study indicate that RCE1 isoform 2 is required for proper %26apos;CaaX%26apos; processing and that USP17 can regulate this via its modulation of RCE1 isoform 2 ubiquitination.

• 出版日期2014-1-15