Journal
ONCOGENE
Volume 21, Issue 47, Pages 7187-7194Publisher
NATURE PUBLISHING GROUP
DOI: 10.1038/sj.onc.1205759
Keywords
Sam68; hnRNP K; RRE; CT element; protein - protein interaction
Funding
- NIAID NIH HHS [AI46240] Funding Source: Medline
- NIGMS NIH HHS [GM05089] Funding Source: Medline
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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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