Proteolytically cleaved MLL subunits are susceptible to distinct degradation pathways.

ABSTRACT: The mixed lineage leukemia (MLL) proto-oncogenic protein is a histone-lysine N-methyltransferase that is produced by proteolytic cleavage and self-association of the respective functionally distinct subunits (MLL(N) and MLL(C)) to form a holocomplex involved in epigenetic transcriptional regulation. On the basis of studies in Drosophila it has been suggested that the separated subunits might also have distinct functions. In this study, we used a genetically engineered mouse line that lacked MLL(C) to show that the MLL(N)-MLL(C) holocomplex is responsible for MLL functions in various developmental processes. The stability of MLL(N) is dependent on its intramolecular interaction with MLL(C), which is mediated through the first and fourth plant homeodomain (PHD) fingers (PHD1 and PHD4) and th

SUBMITTER: Yokoyama A 

PROVIDER: S-EPMC3113671 | biostudies-literature | 2011 Jul

REPOSITORIES: biostudies-literature