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Originally published In Press as doi:10.1074/jbc.M702269200 on August 1, 2007

J. Biol. Chem., Vol. 282, Issue 38, 27887-27896, September 21, 2007
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The Protein Kinase CK2 Phosphorylates SNAP190 to Negatively Regulate SNAPC DNA Binding and Human U6 Transcription by RNA Polymerase III*

Liping Gu, Rhonda Husain-Ponnampalam, Susanne Hoffmann-Benning, and R. William Henry1

From the Department of Biochemistry & Molecular Biology, Michigan State University, East Lansing, Michigan 48824

Human U6 small nuclear RNA gene transcription by RNA polymerase III requires the general transcription factor SNAPC, which binds to human small nuclear RNA core promoter elements and nucleates pre-initiation complex assembly with the Brf2-TFIIIB complex. Multiple components in this pathway are phosphorylated by the protein kinase CK2, including the Bdp1 subunit of the Brf2-TFIIIB complex, and RNA polymerase III, with negative and positive outcomes for U6 transcription, respectively. However, a role for CK2 phosphorylation of SNAPC in U6 transcription has not been defined. In this report, we investigated the role of CK2 in modulating the transcriptional properties of SNAPC and demonstrate that within SNAPC, CK2 phosphorylates the N-terminal half of the SNAP190 subunit at two regions (amino acids 20-63 and 514-545) that each contain multiple CK2 consensus sites. SNAP190 phosphorylation by CK2 inhibits both SNAPC DNA binding and U6 transcription activity. Mutational analyses of SNAP190 support a model wherein CK2 phosphorylation triggers an allosteric inhibition of the SNAP190 Myb DNA binding domain.


Received for publication, March 15, 2007 , and in revised form, July 31, 2007.

* This work was supported by National Institutes of Health Grant R01-GM59805 (to R. W. H.). The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

1 To whom correspondence should be addressed: Dept. of Biochemistry & Molecular Biology, Michigan State University, East Lansing, MI 48824. Tel.: 517-353-3980; Fax: 517-353-9334; E-mail: henryrw{at}msu.edu.


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