Endoplasmic-reticulum-associated Protein Degradation - ERAD and HIV

ERAD and HIV

As described before, the addition of polyubiquitin chains to ERAD substrates is crucial for their export. HIV uses an efficient mechanism to dislocate a single-membrane-spanning host protein, CD4, from the ER and submits it to ERAD. CD4 is normally a stable protein and is not likely to be a target for ERAD. However, HIV produces the membrane protein Vpu that binds to CD4. As Vpu is phosphorylated, it mimics substrates for the E3 complex SCFβTrCP. In cells that are infected with HIV, SCFβTrCP interacts with Vpu and ubiquitinates CD4, which is subsequently degraded by the proteasome. Vpu itself escapes from the degradation.