Reactome | MEN1 binds MLL1 complex

MEN1 binds MLL1 complex

Stable Identifier

R-HSA-9818937

Type

Reaction [binding]

Species

Homo sapiens

Compartment

nucleoplasm

ReviewStatus

5/5

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MEN1 (also known as Menin) associates with the MLL1 complex by binding to the N-terminal region of KMT2A (also known as MLL1 or MLL) (Yokoyama et al. 2005; Caslini et al. 2007; Grembecka et al. 2010; Huang et al. 2012). The N-terminal region of KMT2A contains two putative menin-binding motifs (MBMs) (Grembecka et al. 2010), with residues 6–25 of KMT2A being necessary and sufficient for binding to MEN1 (Huang et al. 2012: recombinant human MEN1 and KMT2A were used). Presence of MEN1-binding motif is necessary for leukemic transformation of mouse myeloid progenitor cells by human leukemia-derived KMT2A fusion proteins and induction of MLL1 target genes HOXA9 and MEIS1 (Caslini et al. 2009). Based on quantitative studies in HeLa cells, MEN1 has 4- to 5-fold-lower abundance in MLL1/MLL2 complexes than KMT2A/KMT2B, indicating that not all MLL1/2 complexes contain MEN1 (van Nuland et al. 2013).

Literature References

PubMed ID	Title	Journal	Year
23508102	Quantitative dissection and stoichiometry determination of the human SET1/MLL histone methyltransferase complexes van Nuland, R, Smits, AH, Pallaki, P, Jansen, PW, Vermeulen, M, Timmers, HT	Mol Cell Biol	2013
22327296	The same pocket in menin binds both MLL and JUND but has opposite effects on transcription Huang, J, Gurung, B, Wan, B, Matkar, S, Veniaminova, NA, Wan, K, Merchant, JL, Hua, X, Lei, M	Nature	2012
20961854	Molecular basis of the mixed lineage leukemia-menin interaction: implications for targeting mixed lineage leukemias Grembecka, J, Belcher, AM, Hartley, T, Cierpicki, T	J Biol Chem	2010
17671196	Interaction of MLL amino terminal sequences with menin is required for transformation Caslini, C, Yang, Z, El-Osta, M, Milne, TA, Slany, RK, Hess, JL	Cancer Res	2007
16239140	The menin tumor suppressor protein is an essential oncogenic cofactor for MLL-associated leukemogenesis Yokoyama, A, Somervaille, TC, Smith, KS, Rozenblatt-Rosen, O, Meyerson, M, Cleary, ML	Cell	2005