Modulation of HSP70 GlcNAc-directed lectin activity by glucose availability and utilization
Modulation of HSP70 GlcNAc-directed lectin activity by glucose availability and utilization
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DOI：
10.1093/glycob/cwj041
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发表时间：
2006-01-01
期刊：
影响因子：
4.3
通讯作者：
Lefebvre, T
中科院分区：
文献类型：
--
作者：
Guinez, C;Losfeld, ME;Lefebvre, T
众所周知，蛋白质质量控制（发生在蛋白质合成后或细胞损伤后）主要由HSP确保，但HSP决定蛋白质是否降解的机制知之甚少。在此框架内，它已被假设，O-GlcNAc，细胞溶质和核特异性糖基化，其功能仍不清楚，可以采取一部分，在保护蛋白质对降解的蛋白质修饰蛋白质本身和蛋白酶体。由于O-GlcNAc的合成与葡萄糖代谢密切相关，而Hsp 70具有GlcNAc结合特性，因此我们研究了Hsp 70和Hsc 70（HSP 70家族的核质形式）的GlcNAc结合活性与葡萄糖利用和利用的关系。因此，我们证明低葡萄糖浓度、2DG抑制葡萄糖利用或CytB抑制葡萄糖转运会导致Hsp 70和Hsc 70凝集素活性增加。有趣的是，Hsp 70和Hsc 70凝集素活性对葡萄糖浓度变化的反应似乎不同：当葡萄糖浓度> 5 mM时，Hsp 70失去其凝集素活性（即，例如，生理葡萄糖浓度），与Hsc 70相反，Hsc 70对类似于5 mM的葡萄糖浓度和在高葡萄糖浓度下表现出最大凝集素活性。这项工作还表明，HSP 70不通过其自身的O-GlcNAc糖基化来调节其GlcNAc结合特性。
It is well-accepted that protein quality control ( occurring either after protein synthesis or after cell damage) is mainly ensured by HSP, but the mechanism by which HSP decides whether the protein will be degraded or not is poorly understood. Within this framework, it has been hypothesized that O-GlcNAc, a cytosolic and nuclear-specific glycosylation whose functions remain unclear, could take a part in the protection of proteins against degradation by modifying both the proteins themselves and the proteasome. Because the synthesis of O-GlcNAc is tightly correlated to glucose metabolism and Hsp70 was endowed with GlcNAc-binding property, we studied the relationship between GlcNAc-binding activity of both Hsp70 and Hsc70 ( the nucleocytoplasmic forms of HSP70 family) and glucose availability and utilization. We thus demonstrated that low glucose concentration, inhibition of glucose utilization with 2DG, or inhibition of glucose transport with CytB led to an increase of Hsp70 and Hsc70 lectin activities. Interestingly, the response of Hsp70 and Hsc70 lectin activities toward variations of glucose concentration appeared different: Hsp70 lost its lectin activity when glucose concentration was > 5 mM ( i. e., physiological glucose concentration) in contrast to Hsc70 that exhibited a maximal lectin activity for glucose concentration similar to 5 mM and at high glucose concentrations. This work also demonstrates that HSP70 does not regulate its GlcNAc-binding properties through its own O-GlcNAc glycosylation.