Journal
CELL CYCLE
Volume 17, Issue 24, Pages 2684-2696Publisher
TAYLOR & FRANCIS INC
DOI: 10.1080/15384101.2018.1553338
Keywords
MLL; H3K4 HMT; mitosis; nucleolus; spindle; centrosome; midbody; MLL fusion proteins
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Funding
- Council of Scientific and Industrial Research [371681/17/EMRII]
- Department of Biotechnology, Ministry of Science and Technology [BT/PR13351/BRB/10/1403/2015]
- Science and Engineering Research Board [EMR/2016/000406]
- CDFD core funds
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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.
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