Please use this identifier to cite or link to this item: http://scholarbank.nus.edu.sg/handle/10635/122845
Title: THE STUDY OF MIXED LINEAGE LEUKEMIA 5 IN CENTROSOME REGULATION AND THE MAINTENANCE OF SPINDLE BIPOLARITY
Authors: ZHAO WEI
Keywords: spindle bipolarity, MLL5, PLK1, centrosome
Issue Date: 29-Sep-2015
Source: ZHAO WEI (2015-09-29). THE STUDY OF MIXED LINEAGE LEUKEMIA 5 IN CENTROSOME REGULATION AND THE MAINTENANCE OF SPINDLE BIPOLARITY. ScholarBank@NUS Repository.
Abstract: FAITHFUL CHROMOSOME SEGREGATION WITH BIPOLAR SPINDLE FORMATION IS CRITICAL FOR THE MAINTENANCE OF GENOMIC STABILITY. MLL5 HAS BEEN DEMONSTRATED TO PLAY VITAL ROLES IN CELL CYCLE PROGRESSION AND THE MAINTENANCE OF GENOMIC STABILITY. HERE, WE IDENTIFY A NOVEL INTERACTION BETWEEN MLL5 AND PLK1 IN THE CYTOSOL, WHICH IS CRUCIAL FOR SUSTAINING SPINDLE BIPOLARITY DURING MITOSIS. KNOCKDOWN OF MLL5 CAUSED ABERRANT PLK1 AGGREGATION THAT LED TO ACENTROSOMAL MICROTUBULE-ORGANIZING CENTER (AMTOC) FORMATION AND SUBSEQUENT SPINDLE MULTIPOLARITY. FURTHER MOLECULAR STUDIES REVEALED THAT THE POLO-BOX DOMAIN (PBD) OF PLK1 INTERACTED WITH A BINDING MOTIF ON MLL5 (THR887-SER888-THR889) AND THIS INTERACTION WAS ESSENTIAL FOR SPINDLE BIPOLARITY. OVEREXPRESSION OF WILD-TYPE MLL5 WAS ABLE TO RESCUE PLK1 MISLOCALIZATION AND AMTOC FORMATION IN MLL5-KD CELLS, WHILE MLL5 MUTANTS INCAPABLE OF INTERACTING WITH THE PBD FAILED TO DO SO. WE HENCE PROPOSE THAT MLL5 PRESERVES SPINDLE BIPOLARITY THROUGH MAINTAINING CYTOSO
URI: http://scholarbank.nus.edu.sg/handle/10635/122845
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