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C-terminus deleted FoxM1 is a dominant negative regulator of transcription

Authors
Kim, Younghwa; Choi, Myoung Ho; Lim, In Kyoung; Park, Tae Jun
Department
Department of Biochemistry & Molecular Biology
Abstract
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 FoxM1C were co-expressed in various cell lines including HeLa, Huh7, A549, MCF7, and MCF10A. Immunoprecipitation assay revealed that FoxM1∆C interacted with wild type FoxM1 and localized in nucleus. Furthermore, FoxM1∆C bound with FoxM1 target gene promoter region and inhibited FoxM1 transcription activity. . Furthermore, FoxM1∆C bound with FoxM1 target gene promoter region and inhibited FoxM1 transcription activity also FoxM1∆C induces instability of FoxM1 protein in G2/M phase. It is speculated that FoxM1∆C might inhibit the function of FoxM1 as the later plays an important role in cell cycle. In summary FoxM1∆C acts like a paralog of FoxM1, however, the exact mechanism of its implication in FoxM1 mediated processes is underway.
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