Figure 4.

VCP/p97 and its function in retroviral protein trafficking. (A) Processing of the MMTV-encoded Rem protein. Rem is synthesized as a precursor at the ER membrane. A portion of Rem is extracted through a retrotranslocon by VCP/p97 and is degraded by the proteasome. The involvement of VCP adapters in this process is unknown. The majority of Rem appears to be cleaved by signal peptidase into a functional HIV-1 Rev-like protein, SP (shown in green), and a C-terminal portion, Rem-CT (shown in magenta). SP requires p97 for extraction from the ER membrane and then traffics to the nucleus to bind MMTV RNA. SP binding is necessary for efficient viral RNA export and expression. (B) Trafficking of Rem-CT. Rem-CT is glycosylated in the ER (Y-shaped structures) and then emerges through ER exit sites (ERES) prior to localization to the ERGIC using the activity of Arf1. Arf1 also is required for trafficking to the Rab7-positive late endosome compartment. Further anterograde trafficking of Rem-CT to the Rab5-positive early endosomes requires VCP/p97. Rem-CT localization to early endosomes or trafficking to the cell surface may allow sequestration or degradation of host transmembrane proteins that participate in innate or adaptive immunity directed against viral infection.