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Oncogenic potential of TAR RNA binding protein TRBP and its regulatory interaction with RNA‐dependent protein kinase PKR
Author(s) -
Benkirane Monsef,
Neuveut Christine,
Chun Rene F.,
Smith Stephen M.,
Samuel Charles E.,
Gatignol Anne,
Jeang KuanTeh
Publication year - 1997
Publication title -
the embo journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 7.484
H-Index - 392
eISSN - 1460-2075
pISSN - 0261-4189
DOI - 10.1093/emboj/16.3.611
Subject(s) - biology , protein kinase r , rna , rna binding protein , kinase , protein kinase a , microbiology and biotechnology , virology , genetics , mitogen activated protein kinase kinase , gene
TAR RNA binding protein (TRBP) belongs to an RNA binding protein family that includes the double‐stranded RNA‐activated protein kinase (PKR), Drosophila Staufen and Xenopus xlrbpa . One member of this family, PKR, is a serine/threonine kinase which has anti‐viral and anti‐proliferative effects. In this study we show that TRBP is a cellular down‐regulator of PKR function. Assaying expression from an infectious HIV‐1 molecular clone, we found that PKR inhibited viral protein synthesis and that over‐expression of TRBP effectively countered this inhibition. In intracellular and in cell‐free assays we show that TRBP directly inhibits PKR autophosphorylation through an RNA binding‐independent pathway. Biologically, TRBP serves a growth‐promoting role; cells that over‐express TRBP exhibit transformed phenotypes. Our results demonstrate the oncogenic potential of TRBP and are consistent with the notion that intracellular PKR function contributes physiologically towards regulating cellular proliferation.