title: EVI1 targets ΔNp63 and upregulates the cyclin dependent kinase inhibitor p21 independent of p53 to delay cell cycle progression and cell proliferation in colon cancer cells.
abstract: Several lines of evidence suggest that specific transcriptional events are involved in cell cycle, proliferation and differentiation processes; however, their deregulation by proto-oncogenes are involved in the development of leukemia and tumors. One such proto-oncogene is ecotropic viral integration site I which can differentially effect cell cycle progression and proliferation, in cell types of different origin. Our data for the first time shows that ecotropic viral integration site I binds to ΔNp63 promoter element directly and down regulates its expression. Down regulation of ΔNp63 induces the expression of p21 in HT-29 cells and also in colon carcinoma cells that do not express p53 including patient samples expressing low level of p53, that eventually delay cell cycle progression at G0/G1 phase. Concomitant silencing of ecotropic viral integration site I from the cells or introduction of ΔNp63 to the cells significantly rescued this phenotype, indicating the growth defect induced by ΔNp63 deficiency to be, at least in part, attributable to ecotropic viral integration site I function. The mutual regulation between ecotropic viral integration site I and ΔNp63 may constitute a novel axis which might affect the downstream pathways in cells that do not express functional p53.
authors.affiliation: Department of Gene Function and Regulation, Institute of Life Sciences, Nalco Square, Bhubaneswar, Odisha, India.
authors.forename: Kasturi Bala
authors.initials: KB
authors.lastname: Nayak
authors.forename: Nivedita
authors.initials: N
authors.lastname: Kuila
authors.forename: Alok
authors.initials: A
authors.lastname: Das Mohapatra
authors.forename: Aditya K
authors.initials: AK
authors.lastname: Panda
authors.forename: Soumen
authors.initials: S
authors.lastname: Chakraborty
mesh_terms: D001483:Base Sequence; D002453:Cell Cycle; D049109:Cell Proliferation; D003110:Colonic Neoplasms / Q000235:genetics / Q000473:pathology*; D050759:Cyclin-Dependent Kinase Inhibitor p21 / Q000235:genetics*; D004268:DNA-Binding Proteins / Q000737:chemistry / Q000378:metabolism*; D015536:Down-Regulation / Q000235:genetics; D015972:Gene Expression Regulation, Neoplastic; D020868:Gene Silencing; D045325:HCT116 Cells; D057809:HEK293 Cells; D019073:HT29 Cells; D006801:Humans; D000074008:MDS1 and EVI1 Complex Locus Protein; D008969:Molecular Sequence Data; D011401:Promoter Regions, Genetic / Q000235:genetics; D011485:Protein Binding / Q000235:genetics; D017434:Protein Structure, Tertiary; D000090063:Proto-Oncogene Mas; D011519:Proto-Oncogenes; D014157:Transcription Factors / Q000737:chemistry / Q000378:metabolism*; D014158:Transcription, Genetic; D016159:Tumor Suppressor Protein p53 / Q000172:deficiency / Q000378:metabolism*; D025521:Tumor Suppressor Proteins / Q000378:metabolism*; D015854:Up-Regulation / Q000235:genetics*; D016335:Zinc Fingers
chemical_list: D050759:Cyclin-Dependent Kinase Inhibitor p21; D004268:DNA-Binding Proteins; C000715470:MAS1 protein, human; D000074008:MDS1 and EVI1 Complex Locus Protein; C063575:MECOM protein, human; D000090063:Proto-Oncogene Mas; C115051:TP63 protein, human; D014157:Transcription Factors; D016159:Tumor Suppressor Protein p53; D025521:Tumor Suppressor Proteins
keywords: Cell cycle; Colon cancer; EVI1; p21; ΔNp63