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J Biol Chem, Vol. 274, Issue 43, 30510-30519, October 22, 1999
Nuclear DEAF-1-related (NUDR) Protein Contains a Novel DNA
Binding Domain and Represses Transcription of the Heterogeneous Nuclear
Ribonucleoprotein A2/B1 Promoter
Rhett J.
Michelson ,
Michael W.
Collard ,
Amy J.
Ziemba ,
Jim
Persinger§,
Blaine
Bartholomew§, and
Jodi I.
Huggenvik
From the Department of Physiology and
§ Department of Medical Biochemistry, Southern Illinois
University School of Medicine, Carbondale, Illinois 62901-6523
Nuclear DEAF-1-related (NUDR) protein is a novel
transcriptional regulator with sequence similarity to developmental and
oncogenic proteins. NUDR protein deletions were used to localize the
DNA binding domain between amino acids 167 and 368, and site-specific DNA photocross-linking indicated at least two sites of protein-DNA contact within this domain. The DNA binding domain contains a proline-rich region and a region with similarity to a Myc-type helix-loop-helix domain but does not include the zinc finger motif at
the C terminus. Deoxyribonuclease I protection assays confirmed the
presence of multiple NUDR binding motifs (TTC(C/G)G) in the heterogeneous nuclear ribonucleoprotein A2/B1 (hnRNP A2/B1) promoter and also in the 5'-untranslated region (UTR) of hNUDR cDNA. NUDR produced a 65-70% repression of the hnRNP A2/B1 promoter activity, and NUDR binding motifs in the 5'-UTR were found to mediate this repression. NUDR-dependent repression was also observed
when the 5'-UTR of NUDR was placed onto a heterologous thymidine kinase promoter in an analogous 5'-UTR position but not when placed upstream of transcription initiation. These results suggest that NUDR may regulate the in vivo expression of hnRNP A2/B1 and NUDR
genes and imply that inactivation of NUDR could contribute to the
overexpression of hnRNP A2/B1 observed in some human cancers.
Copyright © 1999 by The American Society for Biochemistry and Molecular Biology, Inc.

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Copyright © 1999 by the American Society for Biochemistry and Molecular Biology.
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