p53 Is a Master Regulator of Proteostasis in SMARCB1-Deficient Malignant Rhabdoid Tumors.

Document Type

Article

Publication Date

2-11-2019

Keywords

JGM

JAX Source

Cancer Cell 2019 Feb 11; 35(2):204-220.e9

Volume

35

Issue

2

First Page

204

Last Page

220

ISSN

1878-3686

PMID

30753823

DOI

https://doi.org/10.1016/j.ccell.2019.01.006

Abstract

Alterations in chromatin remodeling genes have been increasingly implicated in human oncogenesis. Specifically, the biallelic inactivation of the SWI/SNF subunit SMARCB1 results in the emergence of extremely aggressive pediatric malignancies. Here, we developed embryonic mosaic mouse models of malignant rhabdoid tumors (MRTs) that faithfully recapitulate the clinical-pathological features of the human disease. We demonstrated that SMARCB1-deficient malignancies exhibit dramatic activation of the unfolded protein response (UPR) and ER stress response via a genetically intact MYC-p19

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