title: A novel RCE1 isoform is required for H-Ras plasma membrane localization and is regulated by USP17.
abstract: Processing of the 'CaaX' 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 'CaaX' 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 Lys43 and deubiquitinated by USP17. Collectively, the findings of the present study 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.
authors.affiliation: *School of Pharmacy, Queen's University Belfast, McClay Research Building, 97 Lisburn Road, Belfast BT9 7BL, U.K.
authors.forename: Jakub
authors.initials: J
authors.lastname: Jaworski
authors.forename: Ureshnie
authors.initials: U
authors.lastname: Govender
authors.affiliation: †Centre for Infection and Immunity, School of Medicine, Dentistry and Biomedical Sciences, Queen's University Belfast, Health Sciences Building, 97 Lisburn Road, Belfast BT9 7BL, U.K.
authors.forename: Cheryl
authors.initials: C
authors.lastname: McFarlane
authors.affiliation: †Centre for Infection and Immunity, School of Medicine, Dentistry and Biomedical Sciences, Queen's University Belfast, Health Sciences Building, 97 Lisburn Road, Belfast BT9 7BL, U.K.
authors.forename: Michelle
authors.initials: M
authors.lastname: de la Vega
authors.affiliation: *School of Pharmacy, Queen's University Belfast, McClay Research Building, 97 Lisburn Road, Belfast BT9 7BL, U.K.
authors.forename: Michelle K
authors.initials: MK
authors.lastname: Greene
authors.forename: Neil D
authors.initials: ND
authors.lastname: Rawlings
authors.affiliation: †Centre for Infection and Immunity, School of Medicine, Dentistry and Biomedical Sciences, Queen's University Belfast, Health Sciences Building, 97 Lisburn Road, Belfast BT9 7BL, U.K.
authors.forename: James A
authors.initials: JA
authors.lastname: Johnston
authors.affiliation: *School of Pharmacy, Queen's University Belfast, McClay Research Building, 97 Lisburn Road, Belfast BT9 7BL, U.K.
authors.forename: Christopher J
authors.initials: CJ
authors.lastname: Scott
authors.affiliation: *School of Pharmacy, Queen's University Belfast, McClay Research Building, 97 Lisburn Road, Belfast BT9 7BL, U.K.
authors.forename: James F
authors.initials: JF
authors.lastname: Burrows
mesh_terms: D002462:Cell Membrane / Q000737:chemistry / Q000378:metabolism*; D010450:Endopeptidases / Q000378:metabolism* / Q000502:physiology*; D011905:Genes, ras / Q000502:physiology*; D057809:HEK293 Cells; D006367:HeLa Cells; D006801:Humans; D020033:Protein Isoforms / Q000378:metabolism; D000090063:Proto-Oncogene Mas
chemical_list: C000715470:MAS1 protein, human; D020033:Protein Isoforms; D000090063:Proto-Oncogene Mas; D010450:Endopeptidases; C484854:USP17L2 protein, human; C491326:RCE1 protein, human