Targeting human SET1/MLL family of proteins. (6th March 2017)

• Record Type: Journal Article
• Authors: Vedadi, Masoud; Blazer, Levi; Eram, Mohammad S.; Barsyte‐Lovejoy, Dalia; Arrowsmith, Cheryl H.; Hajian, Taraneh
• Is Part Of: Protein science. Volume 26:Number 4(2017)
• Page Start: 662
• Page End: 676
• Publication Date: 2017-03-06
• Subjects: methyltransferases -- SET1 complexes -- OICR‐9429 -- MM‐401 -- MI‐2‐2 -- EPZ004777 -- EPZ‐5676 -- SGC0946 -- mixed‐lineage leukemia 1 -- leukemogenic rearrangements; Proteins -- Periodicals; 572.6
• DOI: 10.1002/pro.3129
• Languages: English
• ISSNs: 0961-8368

Abstract

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.