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

Processing of the ‘CaaX’ motif found on the carboxy termini of many proteins, including the proto-oncogene Ras, requires the ER resident protease Ras converting enzyme 1 (RCE1) and is necessary for the proper localisation and function of many of these ‘CaaX’ proteins. Here we report that several mammalian species have a novel isoform (Isoform 2) of RCE1 resulting from an alternate splice site and producing an amino 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 localisation in RCE1 null cells. In addition, we show that the deubiquitinating enzyme USP17, previously shown to modulate RCE1 activity, can regulate the abundance and localisation of isoform 2. Furthermore, we show that isoform 2 is ubiquitinated on lysine 43 and deubiquitinated by USP17. Collectively, these findings indicate that RCE1 isoform 2 is required for proper ‘CaaX’ processing and that USP17 can regulate this via its modulation of RCE1 isoform 2 ubiquitination.

Source: BJ Cell - October 17, 2013 Category: Biochemistry Authors: J Jaworski, U Govender, C McFarlane, M de la Vega, M K. Greene, N D. Rawlings, J A. Johnston, C J. Scott, J F. Burrows Tags: BJ Signal Source Type: research