Reactome | Formation of the MLL3 complex

Formation of the MLL3 complex

Stable Identifier

R-HSA-9676254

Type

Reaction [binding]

Species

Homo sapiens

Compartment

nucleoplasm

ReviewStatus

5/5

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KMT2C (also known as MLL3) binds the WRAD complex, consisting of WDR5, RBBP5, ASH2L and DPY30, to form the MLL3 complex. WDR5 plays an important role in the optimal stimulation of MLL3 methyltransferase activity by the RBBP5:ASH2L heterodimer (Zhang et al. 2012). KMT2C can associate with the RBBP5:ASH2L heterodimer in the absence of WDR5 in vitro and form a minimal core complex required for histone mono-methyltransferase activity (Shinsky and Cosgrove 2015). The catalytic activity of this minimal core complex is reduced upon WDR5 binding (Shinsky and Cosgrove 2015). Based on cryoEM structural analysis, different orientation and contacts of KMT2C with the WRAD complex subunits in the MLL3 complex relative to those observed in the MLL1 complex may explain preferential action of this complex as a histone mono-methyltransferase and the limiting effect of WDR5 on KMT2C catalytic activity (Xue et al. 2019).

Literature References

PubMed ID	Title	Journal	Year
26324722	Unique Role of the WD-40 Repeat Protein 5 (WDR5) Subunit within the Mixed Lineage Leukemia 3 (MLL3) Histone Methyltransferase Complex Shinsky, SA, Cosgrove, MS	J Biol Chem	2015
31485071	Structural basis of nucleosome recognition and modification by MLL methyltransferases Xue, H, Yao, T, Cao, M, Zhu, G, Li, Y, Yuan, G, Chen, Y, Lei, M, Huang, J	Nature	2019
22266653	The plasticity of WDR5 peptide-binding cleft enables the binding of the SET1 family of histone methyltransferases Zhang, P, Lee, H, Brunzelle, JS, Couture, JF	Nucleic Acids Res.	2012