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Lethal

Definition:

Polycomb group (PcG) protein that specifically recognizes and binds mono- and dimethyllysine residues on target proteins, therey acting as a 'reader' of a network of post-translational modifications. PcG proteins maintain the transcriptionally repressive state of genes: acts as a chromatin compaction factor by recognizing and binding mono- and dimethylated histone H1b/H1-4 at 'Lys-26' (H1bK26me1 and H1bK26me2) and histone H4 at 'Lys-20' (H4K20me1 and H4K20me2), leading to condense chromatin and repress transcription. Recognizes and binds p53/TP53 monomethylated at 'Lys-382', leading to repress p53/TP53-target genes. Also recognizes and binds RB1/RB monomethylated at 'Lys-860'. Participates in the ETV6-mediated repression. Probably plays a role in cell proliferation. Overexpression induces multinucleated cells, suggesting that it is required to accomplish normal mitosis.

References:

[1]. Patrick Trojer, et al. L3MBTL1, a histone-methylation-dependent chromatin lock. Cell. 2007 Jun 1;129(5):915-28. [Content Brief]

[2]. S Kuphal, et al. Expression of Hugl-1 is strongly reduced in malignant melanoma. Oncogene. 2006 Jan 5;25(1):103-10. [Content Brief]

[3]. Louis A Saddic, et al. Methylation of the retinoblastoma tumor suppressor by SMYD2. J Biol Chem. 2010 Nov 26;285(48):37733-40. [Content Brief]

[4]. N Kalakonda, et al. Histone H4 lysine 20 monomethylation promotes transcriptional repression by L3MBTL1. Oncogene. 2008 Jul 17;27(31):4293-304. [Content Brief]

[5]. Yahong Guo, et al. Methylation-state-specific recognition of histones by the MBT repeat protein L3MBTL2. Nucleic Acids Res. 2009 Apr;37(7):2204-10. [Content Brief]

[6]. Lisandra E West, et al. The MBT repeats of L3MBTL1 link SET8-mediated p53 methylation at lysine 382 to target gene repression. J Biol Chem. 2010 Nov 26;285(48):37725-32. [Content Brief]

[7]. Carl C Schimanski, et al. Reduced expression of Hugl-1, the human homologue of Drosophila tumour suppressor gene lgl, contributes to progression of colorectal cancer. Oncogene. 2005 Apr 28;24(19):3100-9. [Content Brief]

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