A SET-domain-independent role of WRAD complex in cell-cycle regulatory function of mixed lineage leukemia.

Abstract:

:MLL, the trithorax ortholog, is a well-characterized histone 3 lysine 4 methyltransferase that is crucial for proper regulation of the Hox genes during embryonic development. Chromosomal translocations, disrupting the Mll gene, lead to aggressive leukemia with poor prognosis. However, the functions of MLL in cellular processes like cell-cycle regulation are not well studied. Here we show that the MLL has a regulatory role during multiple phases of the cell cycle. RNAi-mediated knockdown reveals that MLL regulates S-phase progression and, proper segregation and cytokinesis during M phase. Using deletions and mutations, we narrow the cell-cycle regulatory role to the C subunit of MLL. Our analysis reveals that the transactivation domain and not the SET domain is important for the S-phase function of MLL. Surprisingly, disruption of MLL-WRAD interaction is sufficient to disrupt proper mitotic progression. These mitotic functions of WRAD are independent of SET domain of MLL and, therefore, define a new role of WRAD in subset of MLL functions. Finally, we address the overlapping and unique roles of the different SET family members in the cell cycle.

journal_name

Nucleic Acids Res

journal_title

Nucleic acids research

authors

Ali A,Veeranki SN,Tyagi S

doi

10.1093/nar/gku458

subject

Has Abstract

pub_date

2014-07-01 00:00:00

pages

7611-24

issue

12

eissn

0305-1048

issn

1362-4962

pii

gku458

journal_volume

42

pub_type

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