Shostak, Kateryna, Jiang, Zheshen, Charloteaux, Benoit, Mayer, Alice, Habraken, Yvette, Tharun, Lars, Klein, Sebastian ORCID: 0000-0002-2188-9377, Xu, Xinyi, Vislovukh, Andrii, Close, Pierre, Florin, Alexandra, Rambow, Florian, Marine, Jean-Christophe ORCID: 0000-0003-2433-9837, Buettner, Reinhard and Chariot, Alain (2020). The X-linked trichothiodystrophy-causing gene RNF113A links the spliceosome to cell survival upon DNA damage. Nat. Commun., 11 (1). LONDON: NATURE PUBLISHING GROUP. ISSN 2041-1723

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Abstract

Prolonged cell survival occurs through the expression of specific protein isoforms generated by alternate splicing of mRNA precursors in cancer cells. How alternate splicing regulates tumor development and resistance to targeted therapies in cancer remain poorly understood. Here we show that RNF113A, whose loss-of-function causes the X-linked trichothiodystrophy, is overexpressed in lung cancer and protects from Cisplatin-dependent cell death. RNF113A is a RNA-binding protein which regulates the splicing of multiple candidates involved in cell survival. RNF113A deficiency triggers cell death upon DNA damage through multiple mechanisms, including apoptosis via the destabilization of the prosurvival protein MCL-1, ferroptosis due to enhanced SAT1 expression, and increased production of ROS due to altered Noxa1 expression. RNF113A deficiency circumvents the resistance to Cisplatin and to BCL-2 inhibitors through the destabilization of MCL-1, which thus defines spliceosome inhibitors as a therapeutic approach to treat tumors showing acquired resistance to specific drugs due to MCL-1 stabilization.

Item Type: Journal Article
Creators:
CreatorsEmailORCIDORCID Put Code
Shostak, KaterynaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Jiang, ZheshenUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Charloteaux, BenoitUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Mayer, AliceUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Habraken, YvetteUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Tharun, LarsUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Klein, SebastianUNSPECIFIEDorcid.org/0000-0002-2188-9377UNSPECIFIED
Xu, XinyiUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Vislovukh, AndriiUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Close, PierreUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Florin, AlexandraUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Rambow, FlorianUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Marine, Jean-ChristopheUNSPECIFIEDorcid.org/0000-0003-2433-9837UNSPECIFIED
Buettner, ReinhardUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Chariot, AlainUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
URN: urn:nbn:de:hbz:38-341293
DOI: 10.1038/s41467-020-15003-7
Journal or Publication Title: Nat. Commun.
Volume: 11
Number: 1
Date: 2020
Publisher: NATURE PUBLISHING GROUP
Place of Publication: LONDON
ISSN: 2041-1723
Language: English
Faculty: Unspecified
Divisions: Unspecified
Subjects: no entry
Uncontrolled Keywords:
KeywordsLanguage
DEPENDENT PROTEIN-KINASE; DOUBLE-STRAND BREAKS; CATALYTIC SUBUNIT; GENOMIC INSTABILITY; SPLICING FACTORS; DOWN-REGULATION; CANCER; REPAIR; AUTOPHOSPHORYLATION; EXPRESSIONMultiple languages
Multidisciplinary SciencesMultiple languages
URI: http://kups.ub.uni-koeln.de/id/eprint/34129

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