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Karole, A.M. and Swathi, C. and Ali, Aamir and Kumari, Nidhi and Tyagi, Shweta (2018) Novel sub-cellular localizations and intra-molecular interactions may define new functions of Mixed Lineage Leukemia protein. Cell Cycle, 17 (24). pp. 2684-2696. ISSN 1538-4101

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Abstract

Mixed-lineage leukemia (MLL) protein is the best-characterized member of SET family of histone 3 lysine 4 methyltransferase, known for its transcriptional-activation role during development. mll gene rearrangements cause multiple kinds of aggressive leukemia in both children and adults. An important 'first' step in understanding the role of MLL in leukemogenesis would be to identify its localization throughout the cell cycle. In order to fully understand the breath of MLL functions in proliferating cells, we have analyzed its sub-cellular localization during the cell cycle. Our results show that MLL localizes to nucleolus and centrosome in interphase. During mitosis, it localizes to centrosomes and midbody in addition to previously reported spindle apparatus. Our results show that MLLN is required to translocate MLLC to the nucleolus. These finding suggest functional roles for MLL in nucleolus and mitosis. We also show how MLL-fusion proteins (MLL-FPs) localize to the same sub-cellular organelles like endogenous MLL. Our results indicate that MLL-fusion proteins may not only disturb the cell homeostasis by gain-of-function of the chimeric protein, but also by interfering with the functions of endogenous MLL.

Item Type: Article
Uncontrolled Keywords: MLL, H3K4 HMT, mitosis, nucleolus, spindle, centrosome, midbody, MLL fusion proteins
Depositing User: Dr P Divakar
Date Deposited: 21 Jan 2019 20:18
Last Modified: 22 Jan 2019 05:40
URI: http://cdfd.sciencecentral.in/id/eprint/878

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