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Apm‐1 interferes with transcriptional factor MIZ‐1 to repress the p21CIP1 gene
Author(s) -
Lee KyungMi,
Choi WonIl,
Yoon JaeHyeon,
Hur ManWook
Publication year - 2010
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.24.1_supplement.678.13
Subject(s) - transcription factor , biology , gene , promoter , transcription (linguistics) , microbiology and biotechnology , reporter gene , fusion protein , immunoprecipitation , carcinogenesis , transcriptional regulation , genetics , gene expression , recombinant dna , linguistics , philosophy
The BTB/POZ family proteins have been implicated in many biological processes, including tumorigenesis, DNA damage responses, cell cycle progression and development. We collected the amino acid sequence information of all 183 human BTB‐POZ domain proteins. Among those proteins, MIZ‐1 regulates expression of several genes, and which can be repressed by c‐Myc. Previous studies identified that MIZ‐1 is associated with regulation of p21 and p15INK4B and binds to the two proximal regulatory elements of p21 promoter. We found that MIZ‐1 regulates transcription of not only p21 but also the other genes of p53 pathway, and induced biological functions of p21. To investigate biological functions of particular POZ domain‐POZ domain interaction involving MIZ‐1, we choose Apm‐1, a potentially important protein interaction partner of MIZ‐1. Apm‐1 is a ubiquitously expressed BTB/POZ‐domain class transcription factor and represses transcription of p21 and ARF, which requires p53. Our co‐immunoprecipitation and GST‐fusion protein pull‐down assay showed that MIZ‐1 interacts with Apm‐1 via their POZ domains directly. We also found that Apm‐1 and MIZ‐1 coexist in the proximal p21 promoter by ChIP. Also reporter assay, quantitative PCR analysis, MTT and FACS analysis suggested that Apm‐1 interferes with transcription activator and cellular regulatory functions of MIZ‐1.