C-terminus deleted FoxM1 is a dominant negative regulator of transcription
Kim, Younghwa; Choi, Myoung Ho; Lim, In Kyoung; Park, Tae Jun
Department of Biochemistry & Molecular Biology, Ajou University School of Medicine
The transcription factor FoxM1 is implicated in a variety of biological processes including regulation of development, cell differentiation and proliferation. FoxM1 is essential for proper mitotic progression and chromosome stability. Aberrant expressions of FoxM1 are linked to human malignancies, such as hepatocellular carcinoma, basal cell carcinoma, breast cancer, lung cancer and colorectal cancer. Recently, we cloned and characterized C-terminus deleted FoxM1 which was isolated from the established cell lines. This protein is a truncated form of FoxM1 which is probably generated by differential splicing. Wild type FoxM1 and FoxM1C were co-expressed in various cell lines including HeLa, Huh7, A549, MCF7, and MCF10A. Immunoprecipitation assay revealed that FoxM1ΔC interacted with wild type FoxM1 and localized in nucleus. Furthermore, FoxM1ΔC bound with FoxM1 target gene promoter region and inhibited FoxM1 transcription activity. . Furthermore, FoxM1ΔC bound with FoxM1 target gene promoter region and inhibited FoxM1 transcription activity also FoxM1ΔC induces instability of FoxM1 protein in G2/M phase. It is speculated that FoxM1ΔC might inhibit the function of FoxM1 as the later plays an important role in cell cycle. In summary FoxM1ΔC acts like a paralog of FoxM1, however, the exact mechanism of its implication in FoxM1 mediated processes is underway.
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