Department of Basic Medical Sciences, Medical College, Xiamen University Xiamen, Fujian, China 361005 ; Abramson Family Cancer Research Institute, Department of Cancer Biology, Abramson Cancer Center, University of Pennsylvania Perelman School of Medicine 421 Curie Blvd., Philadelphia, PA 19104, USA.
Am J Cancer Res. 2013;3(1):96-106. Epub 2013 Jan 18.
Menin acts as contextual a tumor suppressor and a tumor promoter, partly via epigenetic regulation of gene transcription. While menin is phosphorylated, it remains unclear whether wild type menin has other post-translational modifications. Here, we report that menin is SUMOylated by SUMO1 in vivo and in vitro, and the SUMOylation is reduced by a SUMO protease. Lysine 591 of menin was covalently modified by SUMO1 and K591R mutation in menin blocked SUMOylation of the C-terminal part of menin in transfected cells. Full-length menin with K591 mutation was still SUMOylated in vivo, suggesting the existence of multiple SUMOylation sites. Menin K591R mutant or menin-SUMO fusion protein still retains the ability to regulate cell proliferation and the expression of the examined menin target genes.
Menin 作为上下文肿瘤抑制因子和肿瘤促进因子发挥作用，部分是通过表观遗传调控基因转录。虽然 menin 被磷酸化，但目前尚不清楚野生型 menin 是否具有其他翻译后修饰。在这里，我们报告 menin 可被 SUMO1 体内和体外 SUMO 化，SUMO 蛋白酶可降低 SUMO 化。Menin 的赖氨酸 591 被 SUMO1 共价修饰，并且 menin 中的 K591R 突变阻止了 menin 中 C 末端部分的 SUMO 化在转染细胞中。全长 menin 的 K591 突变仍在体内被 SUMO 化，表明存在多个 SUMO 化位点。Menin K591R 突变体或 menin-SUMO 融合蛋白仍保留调节细胞增殖和检查的 menin 靶基因表达的能力。
