Elevated levels of ribosomal proteins eL36 and eL42 control expression of Hsp90 in rhabdomyosarcoma
Citation
Shaikho S, Dobson CC, Naing T, Samanfar B, Moteshareie H, Hajikarimloo M,
Golshani A, Holcik M. Elevated levels of ribosomal proteins eL36 and eL42 control
expression of Hsp90 in rhabdomyosarcoma. Translation (Austin). 2016 Oct
4;4(2):e1244395. doi: 10.1080/21690731.2016.1244395. PubMed PMID: 28090422.
Plain language summary
Hsp90 serves several important biological functions, including folding and maturation of proteins and assembling of steroid hormone receptors and kinases. It plays a key role in maintaining cellular homeostasis by modulating levels of cell cycle regulators, ubiquitin ligases, and aiding in transportation and translocation of proteins.Several studies have investigated the post-transcriptional regulation of Hsp90 expression during stress. but, However, the precise molecular mechanism responsible for Hsp90 upregulation during heat shock, and the genetic regulators of this control are not fully understood.
Here we show that mammalian Hsp90α undergoes selective translation (protein synthesis) during heat shock
Abstract
Mammalian 90 kDa heat shock protein (Hsp90) is a ubiquitous molecular chaperone whose expression is selectively upregulated during stress, although the precise control mechanism of this increase is yet to be fully elucidated. We used polysome profiling to show that Hsp90α mRNA is selectively translated, while global translation is inhibited during heat stress. Furthermore, we have identified 2 ribosomal proteins, eL36 and eL42 that modulate Hsp90α expression under both normal and heat shock conditions. Importantly, we noted that expression of eL36 and eL42 is elevated in a panel of human rhabdomyosarcomas where it drives high expression of Hsp90 and modulates sensitivity of these cells to an Hsp90 inhibitor 17-AAG.