Luman, a new partner of HIV-1 TMgp41, interferes with Tat-mediated transcription of the HIV-1 LTR.
In our search for new partners of the HIV-1 envelope glycoprotein (Env), we found that the cytoplasmic domain of the TMgp41 (TMgp41 CD) subunit of HIV-1 Env interacted with Luman, a transcription factor of the CREB/ATF family. Luman is anchored in the endoplasmic reticulum membrane and subjected to activation by regulated intramembrane proteolysis (RIP). The RIP process permits the release of the activated amino-terminal fragment of Luman into the cytoplasm, and its import into the nucleus. Here, we demonstrate that interaction between the TMgp41 CD and Luman requires a region encompassing the b-Zip and TM domains of Luman and decreases the stability of this factor. Moreover, we found that overexpression of a constitutively active form of Luman in cells transfected with HXB2R HIV-1 provirus decreased the intracellular expression of Gag and Env and led to a decrease in virion release. This negative effect of activated Luman on HIV-1 production was correlated to the inhibition of Tat transactivation of the HIV-1 LTR, which might be related to an interaction of activated Luman with Tat. Altogether, these results show that Luman acts as a partner of two major HIV-1 proteins: the TMgp41 Env subunit and Tat. The interaction between the TMgp41 subunit of Env and Luman affects the stability of the full-length Luman protein, the precursor of the activated, nuclear form of Luman, which acts negatively on Tat-mediated HIV-1 transactivation.
Blot
Guillaume
G
Institut Cochin, Département Maladies Infectieuses, Paris F-75014, France.
Lopez-Vergès
Sandra
S
Treand
Céline
C
Kubat
Nicole J
NJ
Delcroix-Genête
Delphine
D
Emiliani
Stéphane
S
Benarous
Richard
R
Berlioz-Torrent
Clarisse
C
D002478:Cells, Cultured; D017362:Cyclic AMP Response Element-Binding Protein / Q000235:genetics / Q000378:metabolism*; D003593:Cytoplasm / Q000378:metabolism; D004721:Endoplasmic Reticulum / Q000378:metabolism; D015967:Gene Expression Regulation, Viral; D015683:Gene Products, gag / Q000378:metabolism; D015696:Gene Products, tat / Q000235:genetics / Q000378:metabolism*; D015750:Genes, gag; D015700:HIV Envelope Protein gp41 / Q000235:genetics / Q000378:metabolism*; D016325:HIV Long Terminal Repeat / Q000235:genetics*; D015497:HIV-1; D006801:Humans; D047468:Immunoprecipitation; D011533:Proviruses; D012441:Saccharomyces cerevisiae; D014158:Transcription, Genetic; D015533:Transcriptional Activation; D020798:Two-Hybrid System Techniques; D014779:Virus Replication; D054322:tat Gene Products, Human Immunodeficiency Virus
C107941:CREB3 protein, human; D017362:Cyclic AMP Response Element-Binding Protein; D015683:Gene Products, gag; D015696:Gene Products, tat; D015700:HIV Envelope Protein gp41; D054322:tat Gene Products, Human Immunodeficiency Virus