IDENTIFICATION OF A NOVEL CELLULAR COFACTOR FOR THE REV REX CLASS OF RETROVIRAL REGULATORY PROTEINS/

HIV-1 Rev is the prototype of a class of retroviral regulatory protein s that induce the sequence-specific nuclear export of target RNAs. Thi s function requires the Rev activation domain, which is believed to bi nd an essential cellular cofactor. We report the identification of a n ovel human gene product that binds to not only the HIV-1 Rev activatio n domain in vitro and in vivo but also to functionally equivalent doma ins in other Rev and Rex proteins. The Rev/Rex activation domain-bindi ng (Rab) protein occupies a binding site on HIV-I Rev that precisely m atches that predicted by genetic analysis. Rab binds the Rev activatio n domain when Rev is assembled onto its RNA target and can significant ly enhance Rev activity when overexpressed. We conclude that Rab is th e predicted activation domain-specific cofactor for the Rev/Rex class of RNA export factors.