Please use this identifier to cite or link to this item: http://scholarbank.nus.edu.sg/handle/10635/32966
Title: THE STUDY OF MIXED LINEAGE LEUKEMIA 5 IN MITOTIC REGULATION AND MAINTENANCE OF GENOMIC STABILITY.
Authors: LIU JIE
Keywords: Mixed Lineage Leukemia 5, Cell Cycle, Mitosis, MLL5, Phosphorylation, Chromosomal Passenger Complex
Issue Date: 17-Jan-2012
Source: LIU JIE (2012-01-17). THE STUDY OF MIXED LINEAGE LEUKEMIA 5 IN MITOTIC REGULATION AND MAINTENANCE OF GENOMIC STABILITY.. ScholarBank@NUS Repository.
Abstract: Mixed Lineage Leukemia 5 (MLL5) is a versatile nuclear protein involved in many aspects of cellular physiology, including hematopoietic stem cell homeostasis, epigenetic control and cell cycle regulation. This thesis proposes to make a contribution to the current understandings on the molecular function of MLL5 in mitotic regulation. The expression level of MLL5 is relatively constant throughout the cell cycle; however, upon entry into mitosis, MLL5 is phosphorylated and delocalizes from condensed chromosomes in a Cdk1-dependent manner. In addition, perturbation on the phosphorylation modification of MLL5 impedes mitotic entry, suggesting that phosphorylation of MLL5 by Cdk1 is required for mitotic progression. Throughout these studies it was noted that MLL5-depleted cells experience defective cell division and form multinucleus cells, implying a role for MLL5 in maintaining mitotic fidelity. Further investigation reveals that MLL5 maintains the stability of the chromosomal passenger complex (CPC) by functionally interacting with Borealin. Collectively, these data demonstrate that MLL5 contributes to genomic integrity by facilitating the spatial and temporal expression of CPC. Conclusively, this study provides mechanistic insights into the post-translational regulation and molecular signaling of MLL5 at mitotic entry and maintenance of genomic integrity.
URI: http://scholarbank.nus.edu.sg/handle/10635/32966
Appears in Collections:Ph.D Theses (Open)

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