A high-coverage shRNA screen identifies TMEM129 as an E3 ligase involved in ER-associated protein degradation.
Nat Commun
; 5: 3832, 2014 May 08.
Article
en En
| MEDLINE
| ID: mdl-24807418
ABSTRACT
Misfolded ER proteins are retrotranslocated into the cytosol for degradation via the ubiquitin-proteasome system. The human cytomegalovirus protein US11 exploits this ER-associated protein degradation (ERAD) pathway to downregulate HLA class I molecules in virus-infected cells, thereby evading elimination by cytotoxic T-lymphocytes. US11-mediated degradation of HLA class I has been instrumental in the identification of key components of mammalian ERAD, including Derlin-1, p97, VIMP and SEL1L. Despite this, the process governing retrotranslocation of the substrate is still poorly understood. Here using a high-coverage genome-wide shRNA library, we identify the uncharacterized protein TMEM129 and the ubiquitin-conjugating E2 enzyme UBE2J2 to be essential for US11-mediated HLA class I downregulation. TMEM129 is an unconventional C4C4-type RING finger E3 ubiquitin ligase that resides within a complex containing various other ERAD components, including Derlin-1, Derlin-2, VIMP and p97, indicating that TMEM129 is an integral part of the ER-resident dislocation complex mediating US11-induced HLA class I degradation.
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Proteínas Virales
/
Antígenos de Histocompatibilidad Clase I
/
Proteínas de Unión al ARN
/
Interferencia de ARN
/
Enzimas Ubiquitina-Conjugadoras
/
Ubiquitina-Proteína Ligasas
Tipo de estudio:
Risk_factors_studies
Límite:
Humans
Idioma:
En
Revista:
Nat Commun
Asunto de la revista:
BIOLOGIA
/
CIENCIA
Año:
2014
Tipo del documento:
Article
País de afiliación:
Países Bajos