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Protein Sci. 2017 Apr;26(4):662-676. doi: 10.1002/pro.3129. Epub 2017 Mar 6.

Targeting human SET1/MLL family of proteins.

Author information

1
Structural Genomics Consortium, University of Toronto, Toronto, ON, M5G 1L7.
2
Department of Pharmacology and Toxicology, University of Toronto, Toronto, ON, M5S 1A8.
3
Princess Margaret Cancer Centre and Department of Medical Biophysics, University of Toronto, Toronto, ON, M5G 2M9.

Abstract

The SET1 family of proteins, and in particular MLL1, are essential regulators of transcription and key mediators of normal development and disease. Here, we summarize the detailed characterization of the methyltransferase activity of SET1 complexes and the role of the key subunits, WDR5, RbBP5, ASH2L, and DPY30. We present new data on full kinetic characterization of human MLL1, MLL3, SET1A, and SET1B trimeric, tetrameric, and pentameric complexes to elaborate on substrate specificities and compare our findings with what has been reported before. We also review exciting recent work identifying potent inhibitors of oncogenic MLL1 function through disruption of protein-protein interactions within the MLL1 complex.

KEYWORDS:

EPZ-5676; EPZ004777; MI-2-2; MM-401; OICR-9429; SET1 complexes; SGC0946; leukemogenic rearrangements; methyltransferases; mixed-lineage leukemia 1

PMID:
28160335
PMCID:
PMC5368065
DOI:
10.1002/pro.3129
[Indexed for MEDLINE]
Free PMC Article

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