Urologic Oncology Branch, National Cancer Institute, Bethesda, MD, USA.
Future Oncol. 2012 Aug;8(8):939-42. doi: 10.2217/fon.12.80.
The molecular chaperone HSP90, in concert with the co-chaperone CDC37, facilitates the maturation and modulates the activity of a variety of protein kinases. In this article, Gaude and colleagues described the dual activities of the HSP90-CDC37 chaperone machinery in maintaining the stability while inhibiting the activity of LKB1 kinase. LKB1 in complex with HSP90-CDC37 has a longer half-life but is incapable of autophosphorylation, and its kinase activity is increased upon HSP90 inhibition. Dissociation of HSP90 from LKB1 results in its interaction with HSP/HSC70. HSP/HSC70 recruits the ubiquitin ligase CHIP, which ubiquitinates LKB1, leading to its proteasome-mediated degradation. These data emphasize the versatile roles of molecular chaperones associated with LKB1 and warrant future studies to characterize the clinical relevance of these observations.
分子伴侣 HSP90 与共伴侣 CDC37 协同作用，促进多种蛋白激酶的成熟和调节其活性。在这篇文章中，Gaude 及其同事描述了 HSP90-CDC37 伴侣机制在维持 LKB1 激酶稳定性的同时抑制其活性的双重作用。与 HSP90-CDC37 形成复合物的 LKB1 半衰期更长，但不能进行自身磷酸化，其激酶活性在 HSP90 抑制时增加。HSP90 从 LKB1 上解离导致其与 HSP/HSC70 相互作用。HSP/HSC70 招募泛素连接酶 CHIP，后者泛素化 LKB1，导致其被蛋白酶体介导降解。这些数据强调了与 LKB1 相关的分子伴侣的多种作用，并需要进一步的研究来描述这些观察结果的临床相关性。
