Asset Details
Do you wish to reserve the book?
Calreticulin Ins5 and Del52 mutations impair unfolded protein and oxidative stress responses in K562 cells expressing CALR mutants
Hey, we have placed the reservation for you!
By the way, why not check out events that you can attend while you pick your title.
Oops! Something went wrong.
Looks like we were not able to place the reservation. Kindly try again later.
Are you sure you want to remove the book from the shelf?
Calreticulin Ins5 and Del52 mutations impair unfolded protein and oxidative stress responses in K562 cells expressing CALR mutants
Do you wish to request the book?
Calreticulin Ins5 and Del52 mutations impair unfolded protein and oxidative stress responses in K562 cells expressing CALR mutants
Please be aware that the book you have requested cannot be checked out. If you would like to checkout this book, you can reserve another copy
We have requested the book for you!
Your request is successful and it will be processed during the Library working hours. Please check the status of your request in My Requests.
Oops! Something went wrong.
Looks like we were not able to place your request. Kindly try again later.
Journal Article
Calreticulin Ins5 and Del52 mutations impair unfolded protein and oxidative stress responses in K562 cells expressing CALR mutants
2019
Overview
Somatic mutations of calreticulin (CALR) have been described in approximately 60–80% of JAK2 and MPL unmutated Essential Thrombocythemia and Primary Myelofibrosis patients. CALR is an endoplasmic reticulum (ER) chaperone responsible for proper protein folding and calcium retention. Recent data demonstrated that the TPO receptor (MPL) is essential for the development of CALR mutant-driven Myeloproliferative Neoplasms (MPNs). However, the precise mechanism of action of CALR mutants haven’t been fully unraveled. In this study, we showed that CALR mutants impair the ability to respond to the ER stress and reduce the activation of the pro-apoptotic pathway of the unfolded protein response (UPR). Moreover, our data demonstrated that CALR mutations induce increased sensitivity to oxidative stress, leading to increase oxidative DNA damage. We finally demonstrated that the downmodulation of OXR1 in CALR-mutated cells could be one of the molecular mechanisms responsible for the increased sensitivity to oxidative stress mediated by mutant CALR. Altogether, our data identify novel mechanisms collaborating with MPL activation in CALR-mediated cellular transformation. CALR mutants negatively impact on the capability of cells to respond to oxidative stress leading to genomic instability and on the ability to react to ER stress, causing resistance to UPR-induced apoptosis.
Publisher
Nature Publishing Group UK,Nature Publishing Group
Subject
/ 13/2
/ 13/31
/ 13/89
/ 38/39
/ 42/44
/ 82/1
/ 82/80
/ 96/95
/ Calcium
/ Cell Transformation, Neoplastic - genetics
/ Endoplasmic Reticulum Stress - genetics
/ Humanities and Social Sciences
/ Humans
/ Mitochondrial Proteins - antagonists & inhibitors
/ Mitochondrial Proteins - genetics
/ Mutant Proteins - metabolism
/ Mutants
/ Mutation
/ Phenanthrenes - pharmacology
/ Primary Myelofibrosis - genetics
/ Primary Myelofibrosis - metabolism
/ Proteins
/ Recombinant Proteins - genetics
/ Recombinant Proteins - metabolism
/ Science
/ Superoxide Dismutase - metabolism
/ Thrombocythemia, Essential - genetics
