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Functional interaction of Sam68 and heterogeneous nuclear ribonucleoprotein K

Oncogene volume 21, pages 7187–7194 (2002)Cite this article

Abstract

Sam68 is a target of the c-Src tyrosine kinase. We previously showed that overexpression of Sam68 functionally substitutes for, as well as synergies with, HIV-1 Rev in Rev-response element (RRE)-mediated gene expression and virus replication. Here we describe the identification of heterogeneous nuclear ribonucleoprotein K (hnRNP K) as a protein that specifically interacts with Sam68 in vitro and in vivo. HnRNP K did not bind to RRE-RNA directly, but formed a super complex with Sam68 and RRE in vitro. RNase treatment did not change the strength of binding of hnRNP K to Sam68. We demonstrated that hnRNP K significantly inhibited Sam68-mediated, but not Rev-mediated, RRE-dependent gene expression. We further showed that Sam68, but not a non-functional mutant Sam68p21, inhibited transcriptional activation of CT element by hnRNP K. Interestingly, the Sam68p21 with a single amino acid substitution in the nuclear localization domain exhibited less affinity for hnRNP K in vitro. We propose that the direct interaction of Sam68 and hnRNP K adversely affect the activities of both proteins in signal transduction pathways of both transcriptional and post-transcriptional events.

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Acknowledgements

This work was supported by NIH grant GM05089 and a grant from the University Wide AIDS Research Program to F Wong-Staal, and AI46240 to TR Reddy.

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Author notes

  1. Jian-Ping Yang and Thipparthi R Reddy: Jian-Ping Yang and Thipparthi R Reddy have contributed equally to this work

Authors and Affiliations

  1. Department of Biology, University of California, San Diego, La Jolla, 92093-0665, California, CA, USA

    Jian-Ping Yang, Ky T Truong & Flossie Wong-Staal

  2. Department of Medicine, University of California, San Diego, La Jolla, 92093-0665, California, CA, USA

    Jian-Ping Yang, Ky T Truong & Flossie Wong-Staal

  3. Department of Immunology and Microbiology, School of Medicine, Wayne State University, Detroit, 48201, Michigan, MI, USA

    Thipparthi R Reddy & Modem Suhasini

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  1. Jian-Ping Yang
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Correspondence to Flossie Wong-Staal.

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Yang, JP., Reddy, T., Truong, K. et al. Functional interaction of Sam68 and heterogeneous nuclear ribonucleoprotein K. Oncogene 21, 7187–7194 (2002). https://doi.org/10.1038/sj.onc.1205759

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