A new role for a known protein
doi:10.1038/nindia.2017.95 Published online 31 July 2017
Scientists report a new function for a protein involved in blood cancer. The mixed-lineage leukemia (MLL) protein, known to activate genes through methylation in patients with acute leukemia, also regulates how chromosomes align during cell division, researchers at the Centre for DNA Fingerprinting and Diagnostics in Hyderabad report1.
When a cell divides, a network of proteins and microtubules form a spindle apparatus. The spindle pulls apart copies of chromosomes, allowing the cell to split into two genetically identical daughter cells. The researchers were surprised to find MLL interacting with proteins of the spindle.
In a series of time lapse movies, the researchers observed MLL labeled with green fluorescent protein on the chromosomes as well as associating directly with the spindle. They conducted antibody experiments to confirm that MLL indeed interacted with the spindle.
When they suppressed MLL, it resulted in compromised spindle formation, misaligned chromosomes, and stalled cellular division. This was further evidence that MLL plays a part in the spindle, separating chromosomes. Using mass spectrometry, the group identified two motor proteins — kinesin and dynein — that make up microtubules, as potential MLL spindle binding partners.
“The fact that we are now open to embrace new roles of MLL in cellular processes, and that MLL can have more than a histone methylation function are the most valuable take home messages from this study,” said Shweta Tyagi, lead author.
1. Ali, A. et al. MLL/WDR5 complex regulates Kif2A localization to ensure chromosome congression and proper spindle assembly during mitosis. Developmental Cell (2017) doi: 10.1016/j.devcel.2017.05.023