Please use this identifier to cite or link to this item: http://scholarbank.nus.edu.sg/handle/10635/36383
Title: THE STUDY OF A NOVEL MIXED LINEAGE LEUKEMIA 5 ISOFORM AND ITS ASSOCIATION WITH HUMAN PAPILLOMAVIRUS 16/18 - RELATED HUMAN CERVICAL CANCERS
Authors: YEW CHOW WENN
Keywords: MLL5, HPV, cervical cancers, E6, E7
Issue Date: 24-Aug-2012
Source: YEW CHOW WENN (2012-08-24). THE STUDY OF A NOVEL MIXED LINEAGE LEUKEMIA 5 ISOFORM AND ITS ASSOCIATION WITH HUMAN PAPILLOMAVIRUS 16/18 - RELATED HUMAN CERVICAL CANCERS. ScholarBank@NUS Repository.
Abstract: Human papillomavirus (HPV) is the primary cause of human cervical cancer. The viral proteins E6 and E7 are essential to transform non-cancerous epithelial cells into cancerous carcinomas by targeting key tumour suppressors p53 and retinoblastoma proteins. In this study, we defined a novel Mixed Lineage Leukemia 5 isoform (MLL5ß) as a specific and critical regulator of E6 and E7 transcription in cervical carcinoma cells. MLL5ß is present exclusively in HPV16/18-positive cells including human primary cervical carcinoma specimens. Interaction of MLL5ß with the AP-1 binding site at the distal region of HPV18 long control region led to activation of E6/E7 transcription. Conversely, RNAi-mediated knockdown of MLL5ß downregulated both E6 and E7 expression. MLL5ß downregulation was sufficient to restore p53 protein levels and reduce Rb phosphorylation, thereby re-activating apoptosis and cell cycle checkpoints. Our work highlights the potential of MLL5ß as a biomarker and new therapeutic target in primary HPV-induced cervical cancers.
URI: http://scholarbank.nus.edu.sg/handle/10635/36383
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