HIV-1 Tat interacts with LIS1 protein.
BACKGROUND
HIV-1 Tat activates transcription of HIV-1 viral genes by inducing phosphorylation of the C-terminal domain (CTD) of RNA polymerase II (RNAPII). Tat can also disturb cellular metabolism by inhibiting proliferation of antigen-specific T lymphocytes and by inducing cellular apoptosis. Tat-induced apoptosis of T-cells is attributed, in part, to the distortion of microtubules polymerization. LIS1 is a microtubule-associated protein that facilitates microtubule polymerization.


RESULTS
We identified here LIS1 as a Tat-interacting protein during extensive biochemical fractionation of T-cell extracts. We found several proteins to co-purify with a Tat-associated RNAPII CTD kinase activity including LIS1, CDK7, cyclin H, and MAT1. Tat interacted with LIS1 but not with CDK7, cyclin H or MAT1 in vitro. LIS1 also co-immunoprecipitated with Tat expressed in HeLa cells. Further, LIS1 interacted with Tat in a yeast two-hybrid system.


CONCLUSIONS
Our results indicate that Tat interacts with LIS1 in vitro and in vivo and that this interaction might contribute to the effect of Tat on microtubule formation.
Epie
Nicolas
N
Center for Sickle Cell Disease, Howard University, Washington, DC 20059, USA. nepie@howard.edu
Ammosova
Tatyana
T
Sapir
Tamar
T
Voloshin
Yaroslav
Y
Lane
William S
WS
Turner
Willie
W
Reiner
Orly
O
Nekhai
Sergei
S
D043203:1-Alkyl-2-acetylglycerophosphocholine Esterase; D056748:Cyclin H; D018844:Cyclin-Dependent Kinases / Q000378:metabolism; D016213:Cyclins / Q000378:metabolism; D015696:Gene Products, tat / Q000378:metabolism*; D015497:HIV-1 / Q000378:metabolism / Q000472:pathogenicity; D006367:HeLa Cells; D006801:Humans; D019169:Jurkat Cells; D008869:Microtubule-Associated Proteins / Q000378:metabolism*; D012319:RNA Polymerase II / Q000378:metabolism; D020798:Two-Hybrid System Techniques; D054322:tat Gene Products, Human Immunodeficiency Virus; D000095043:Cyclin-Dependent Kinase-Activating Kinase
C534751:CCNH protein, human; D056748:Cyclin H; D016213:Cyclins; D015696:Gene Products, tat; D008869:Microtubule-Associated Proteins; D054322:tat Gene Products, Human Immunodeficiency Virus; D018844:Cyclin-Dependent Kinases; D012319:RNA Polymerase II; D043203:1-Alkyl-2-acetylglycerophosphocholine Esterase; C084102:PAFAH1B1 protein, human; D000095043:Cyclin-Dependent Kinase-Activating Kinase