A novel nuclear zinc finger protein EZI enhances nuclear retention and transactivation of STAT3.
A novel cDNA EZI isolated as an oncostatin M- inducible gene encoded a protein containing 12 C2H2-type zinc fingers. EZI was found to transactivate the promoters that are also responsive to STAT3 and activated the acute phase response element (APRE) synergistically with STAT3. Co-immunoprecipitation demonstrated the association of EZI with STAT3, which was mediated by the N-terminal region (1-183) of EZI. The EZI mutant lacking this region showed reduced transcriptional activity, indicating that EZI and STAT3 function cooperatively through physical interaction. While EZI predominantly localized in the nucleus and enhanced the nuclear localization of STAT3, the EZI mutant lacking 11 zinc finger motifs failed to translocate into the nucleus and also inhibited nuclear localization of STAT3 as well as STAT3-mediated transactivation. These results indicate that EZI is a novel nuclear zinc finger protein that augments STAT3 activity by keeping it in the nucleus.
Nakayama
Koh
K
Institute of Molecular and Cellular Biosciences, The University of Tokyo, Yayoi, Bunkyo-ku, Tokyo 113-0032, Japan.
Kim
Kyung-Woon
KW
Miyajima
Atsushi
A
D016475:3T3 Cells; D021581:Active Transport, Cell Nucleus / Q000502:physiology; D000595:Amino Acid Sequence; D000818:Animals; D019556:COS Cells; D002467:Cell Nucleus / Q000378:metabolism; D002522:Chlorocebus aethiops; D004247:DNA / Q000378:metabolism; D018076:DNA, Complementary / Q000235:genetics; D004268:DNA-Binding Proteins / Q000378:metabolism*; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation / Q000187:drug effects; D051379:Mice; D008969:Molecular Sequence Data; D009687:Nuclear Proteins / Q000235:genetics / Q000502:physiology*; D053683:Oncostatin M; D010455:Peptides / Q000494:pharmacology; D011401:Promoter Regions, Genetic; D011993:Recombinant Fusion Proteins / Q000502:physiology; D050796:STAT3 Transcription Factor; D013382:Subtraction Technique; D015534:Trans-Activators / Q000378:metabolism*; D014157:Transcription Factors / Q000235:genetics / Q000502:physiology*; D015533:Transcriptional Activation / Q000502:physiology; D016335:Zinc Fingers / Q000235:genetics / Q000502:physiology*
D018076:DNA, Complementary; D004268:DNA-Binding Proteins; C469741:EZI protein, mouse; D009687:Nuclear Proteins; C508352:Osm protein, mouse; D010455:Peptides; D011993:Recombinant Fusion Proteins; D050796:STAT3 Transcription Factor; C494087:Stat3 protein, mouse; D015534:Trans-Activators; D014157:Transcription Factors; D053683:Oncostatin M; D004247:DNA