Document 0906
 DOCN  M9440906
 TI    HIV-1 transactivator protein Tat induces proliferation and TGF beta
       expression in human articular chondrocytes.
 DT    9404
 AU    Lotz M; Clark-Lewis I; Ganu V; Sam and Rose Stein Institute for Research
       on Aging, University of; California, San Diego 92093.
 SO    J Cell Biol. 1994 Feb;124(3):365-71. Unique Identifier : AIDSLINE
       MED/94124631
 AB    The human immunodeficiency virus-1 (HIV-1) protein Tat binds to cell
       surface antigens and can regulate cellular responses. Tat has similar
       immunosuppressive effects as transforming growth factor-beta (TGF beta)
       and both inhibit lymphocyte proliferation. TGF beta is expressed by
       primary human articular chondrocytes and is their most potent growth
       factor. The present study analyzed the interactions of TGF beta and HIV
       Tat in the regulation of human articular chondrocytes. Synthetic or
       recombinant full-length Tat (1-86) induced chondrocyte proliferation and
       this was of similar magnitude as the response to TGF beta. Tat peptides
       that did not contain the RGD motif had similar chondrocyte stimulatory
       activity as full-length Tat. Among a series of Tat peptides, peptide
       38-62 which contains the basic domain was the only one active,
       suggesting that this region is responsible for the effects on
       chondrocyte proliferation. Full-length Tat and peptide 38-62 synergized
       with TGF beta and induced proliferative responses that were greater than
       those obtained with any combination of the known chondrocyte growth
       factors. Further characterization of the interactions between Tat and
       TGF beta showed that Tat increased synthesis and TGF beta activity and
       TGF beta 1 mRNA levels. The stimulatory effects of Tat and peptide 38-62
       on chondrocyte proliferation were reduced by neutralizing antibodies to
       TGF beta and by TGF beta antisense oligonucleotides. These results
       identify a virally encoded protein and a synthetic peptide derived from
       it as novel and potent chondrocyte growth stimuli which act at least in
       part through the induction of TGF beta.
 DE    Base Sequence  Cartilage, Articular/CYTOLOGY/*DRUG EFFECTS/METABOLISM
       Cell Division/DRUG EFFECTS  Cells, Cultured  Fibroblasts/CYTOLOGY/DRUG
       EFFECTS  Gene Products, tat/*PHARMACOLOGY  Human  Molecular Sequence
       Data  Recombinant Proteins/PHARMACOLOGY  RNA,
       Messenger/GENETICS/METABOLISM  Support, U.S. Gov't, P.H.S.  Transforming
       Growth Factor beta/*BIOSYNTHESIS  JOURNAL ARTICLE

       SOURCE: National Library of Medicine.  NOTICE: This material may be
       protected by Copyright Law (Title 17, U.S.Code).