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Lysines residing in putative Small Ubiquitin-like MOdifier (SUMO) motifs regulate fate and function of 37 KDa laminin receptor
Biochimie ( IF 3.3 ) Pub Date : 2018-10-10 , DOI: 10.1016/j.biochi.2018.10.003
Charles Samuel Umbaugh , Marxa L. Figueiredo

There is a putative precursor to mature receptor relationship between 37 Laminin Receptor (LR) and 67 LR. As such, the pair are frequently referred to as a single entity, the 37/67 kDa Laminin Receptor (37/67 LR) and 67 LR was identified as a laminin binding entity. 37/67 LR has been of clinical interest for many years, as 37/67 LR is a prognostic indicator for many cancers including breast, lung, colon, and prostate. However, the genesis of 67 LR is controversial, and confounded by its stability under SDS-PAGE conditions, a lack of splice variants, and the existence of post-translational modifications that cannot account for the mass discrepancy between 37 and 67 LR. In the present work, we mutated potential SUMO motif sites (Lysine residues) in 37 LR and generated a series of 37 LR-expressing plasmids with a C-terminal histidine tag. We report an inability to detect 67 LR formation, suggesting that SUMOylation does not appear to directly occur at the lysine residues proposed. However, the work revealed that these lysine mutations still appear to be important and can impact the fate and function of 37 LR, by impairing half-life and steady state pre-mRNA levels. These results suggest that the Lys residues within putative SUMO motifs of 37 LR are important for 37 LR function.



中文翻译:

驻留在假定的小泛素样修饰子(SUMO)基序中的赖氨酸调节37 KDa层粘连蛋白受体的命运和功能

37层粘连蛋白受体(LR)和67 LR之间存在成熟受体关系的推定前体。因此,该对通常称为单个实体,将37/67 kDa层粘连蛋白受体(37/67 LR)和67 LR鉴定为层粘连蛋白结合实体。37/67 LR已引起临床关注多年,因为37/67 LR是许多癌症(包括乳腺癌,肺癌,结肠癌和前列腺癌)的预后指标。然而,67 LR的起源是有争议的,并因其在SDS-PAGE条件下的稳定性,缺乏剪接变体以及翻译后修饰的存在而感到困惑,这些修饰不能解释37和67 LR之间的质量差异。在目前的工作中,我们突变了37个LR中潜在的SUMO基序位点(赖氨酸残基),并生成了一系列带有C端组氨酸标签的37个LR表达质粒。我们报告无法检测到67 LR的形成,这表明SUMOylation似乎不直接发生在建议的赖氨酸残基上。但是,这项工作表明,这些赖氨酸突变似乎仍然很重要,并且可以通过损害半衰期和稳态前mRNA水平来影响37 LR的命运和功能。这些结果表明,在37 LR的假定SUMO基序内的Lys残基对37 LR功能很重要。

更新日期:2018-10-10
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