Nef Mediated CD4 Down-regulation Authored: Gillespie, ME, 2007-07-25 19:42:36 GENE ONTOLOGYGO:0050690 Pubmed11264384 Pubmed2014052 Pubmed7831289 Pubmed8124721 Pubmed8756680 Reactome Database ID Release 43167590 Reactome, http://www.reactome.org ReactomeREACT_11166 Reviewed: Skowronski, J, 2007-08-07 14:33:41 The presence of Nef accelerates endocytosis and lysosomal degradation of the transmembrane glycoprotein CD4. CD4 has its own internalization motif, though this motif is normally concealed by CD4 interaction with Lck, a tyrosine kinase. Nef is known to disrupt this interaction and then facilitate a cascade of protein interactions that ultimately result in the degradation of internalized CD4 protein. The final set of protein interactions that direct Nef to the beta-subunit of the COPI coatomers are at this time unclear.<br><br>A benefit for the virus from CD4 down-modulation is abolition of interaction between the receptor and the Env protein of the budding virus, which likely increases HIV release from infected cell as well as infectivity of viral particles. PathwayStep3657 PathwayStep3658 PathwayStep3659 PathwayStep3656 PathwayStep3660 Nef mediated disruption of CD4:Lck Complex Internalization of the CD4:Nef:AP-2 Complex:v-ATPase Complex Formation of CD4:Nef:AP-2 Complex:v-ATPase Complex Formation of a Nef:ARF1:CD4 complex Degradation of CD4