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Publication : Physical and functional interaction between the transcriptional cofactor CBP and the KH domain protein Sam68.

First Author  Hong W Year  2002
Journal  Mol Cancer Res Volume  1
Issue  1 Pages  48-55
PubMed ID  12496368 Mgi Jnum  J:80589
Mgi Id  MGI:2446384 Citation  Hong W, et al. (2002) Physical and functional interaction between the transcriptional cofactor CBP and the KH domain protein Sam68. Mol Cancer Res 1(1):48-55
abstractText  CBP is a multifunctional transcriptional cofactor with tumor suppressor activity. The CH3 domain of CBP binds numerous transcription factors and several viral oncoproteins. We identified the Src substrate and RNA-binding protein Sam68 as novel CH3-binding protein. Sam68 binds the CH3 domain in part through a conserved FXD/EXXXL motif that is shared among several CH3-binding proteins, including the adenoviral oncoprotein E1A and the tumor suppressor p53. Sam68 and CBP interact in vivo and colocalize in nuclear sub-domains. Sam68 has potent transcriptional repression activity that is independent of its RNA binding activity, which suggests that RNA processing and regulation of gene expression by Sam68 are separable functions. Consistent with this, CBP did not stimulate the ability of Sam68 to promote Rev response element-containing mRNA export. Interestingly, Sam68 can regulate RNA processing in the absence of a Rev response element, suggesting that Sam68 functions through a novel RNA element. Together, these findings reveal a previously unidentified function for Sam68 as a transcriptional repressor and suggest that Sam68 might link cellular signaling pathways with components of the transcriptional machinery.
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