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J Virol, May 1998, p. 4448-4453, Vol. 72, No. 5
Division of Molecular Virology, Baylor
College of Medicine, Houston, Texas
Received 14 October 1997/Accepted 3 February 1998
The human cdc2-related kinase PITALRE is the catalytic component of
TAK, the Tat-associated kinase. Previously, we have proposed that TAK
is a cellular factor that mediates Tat transactivation function. Here
we demonstrate that transient overexpression of PITALRE specifically
squelches Tat-1 activation of both a transfected and an
integrated human immunodeficiency virus type 1 (HIV-1) long terminal
repeat (LTR), suggesting that PITALRE mediates Tat function as a
multiprotein complex. A catalytic mutant of PITALRE, D167N, was
found to be more efficient than wild-type PITALRE in squelching Tat
transactivation. Neither wild-type PITALRE nor D167N was able to
squelch transactivation of the human T-cell leukemia type 1 LTR by the
Tax protein. Additionally, we show that artificial targeting of PITALRE
to a nascent RNA element, in the absence of Tat, activated HIV-1 LTR
expression. These results indicate that a PITALRE-containing complex
mediates transactivation by Tat and suggest that Tat proteins function
by localizing such a PITALRE-containing complex to the site of
the transcribing provirus.
0022-538X/98/$04.00+0
Copyright © 1998, American Society for Microbiology. All rights reserved.
PITALRE, the Catalytic Subunit of TAK, Is Required for Human
Immunodeficiency Virus Tat Transactivation In Vivo
*
Corresponding author. Mailing address: Division of
Molecular Virology, Baylor College of Medicine, One Baylor Plaza,
Houston, TX 77030. Phone: (713) 798-5774. Fax: (713)
798-3490. E-mail: arice{at}bcm.tmc.edu.
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