TULA proteins bind to ABCE-1, a host factor of HIV-1 assembly, and inhibit HIV-1 biogenesis in a UBA-dependent fashion.
TULA, a recently identified UBA- and SH3-containing protein, has previously been shown to regulate cell signaling through protein tyrosine kinases. In order to search for novel functions of TULA, we identified, using mass spectrometry, proteins associated with TULA. ABCE-1 also known as RLI and HP68, a host factor of HIV-1 assembly, was found among TULA-associated proteins in these experiments. Considering an important role of ABCE-1 in HIV-1 assembly, we were compelled to analyze the effect of TULA on HIV-1 biogenesis. Our study provides evidence that TULA proteins substantially inhibit production of both sub-genomic and full-length HIV-1 viral particles and that the effect of TULA is dependent on UBA domain-mediated interactions. The primary role of ABCE-1 in the effect of TULA appears to be the recruitment of TULA to the sites of HIV-1 assembly where TULA interferes with the late steps of the HIV-1 life cycle, most likely by disrupting essential ubiquitylation-dependent events that remain to be identified.
Smirnova
Evgeniya V
EV
Department of Microbiology and Immunology, Temple University School of Medicine, Philadelphia, PA 19140, USA.
Collingwood
Therese S
TS
Bisbal
Catherine
C
Tsygankova
Oxana M
OM
Bogush
Marina
M
Meinkoth
Judy L
JL
Henderson
Earl E
EE
Annan
Roland S
RS
Tsygankov
Alexander Y
AY
D018528:ATP-Binding Cassette Transporters / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D000595:Amino Acid Sequence; D002352:Carrier Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D002460:Cell Line; D018833:Chaperonins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D015683:Gene Products, gag / Q000235:genetics / Q000378:metabolism; D015497:HIV-1 / Q000187:drug effects / Q000502:physiology*; D006367:HeLa Cells; D006801:Humans; D047468:Immunoprecipitation; D013058:Mass Spectrometry; D008565:Membrane Proteins; D008969:Molecular Sequence Data; D014162:Transfection; D025801:Ubiquitin / Q000235:genetics / Q000378:metabolism*; D019065:Virus Assembly
C501917:ABCE1 protein, human; D018528:ATP-Binding Cassette Transporters; C489394:CLIP4 protein, human; D002352:Carrier Proteins; D015683:Gene Products, gag; D008565:Membrane Proteins; D025801:Ubiquitin; D018833:Chaperonins