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Intracellular C4BPA Levels Regulate NF-κB-Dependent Apoptosis

Olcina, Monica M. and Kim, Ryan K. and Balanis, Nikolas G. and Li, Caiyun Grace and von Eyben, Rie and Graeber, Thomas G. and Ricklin, Daniel and Stucki, Manuel and Giaccia, Amato J.. (2020) Intracellular C4BPA Levels Regulate NF-κB-Dependent Apoptosis. iScience, 23 (10). p. 101594.

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Official URL: https://edoc.unibas.ch/81053/

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Abstract

The importance of innate immunity in cancer is increasingly being recognized with recent reports suggesting tumor cell-intrinsic intracellular functions for innate immunity proteins. However, such functions are often poorly understood, and it is unclear whether these are affected by patient-specific mutations. Here, we show that C4b-binding protein alpha chain (C4BPA), typically thought to reside in the extracellular space, is expressed intracellularly in cancer cells, where it interacts with the NF-κB family member RelA and regulates apoptosis. Interestingly, intracellular C4BPA expression is regulated in a stress- and mutation-dependent manner and; C4BPA; mutations are associated with improved cancer survival outcome. Using cell lines harboring patient-specific; C4BPA; mutations, we show that increasing intracellular C4BPA levels correlate with sensitivity to oxaliplatin-induced apoptosis; in vitro; and; in vivo; . Mechanistically, sensitive; C4BPA; mutants display increased IκBα expression and increased inhibitory IκBα-RelA complex stability. These data suggest a non-canonical intracellular role for C4BPA in regulating NF-κB-dependent apoptosis.
Faculties and Departments:05 Faculty of Science > Departement Pharmazeutische Wissenschaften > Pharmazie > Molekulare Pharmazie (Ricklin)
UniBasel Contributors:Ricklin, Daniel
Item Type:Article, refereed
Article Subtype:Research Article
Publisher:Cell Press
ISSN:2589-0042
Note:Publication type according to Uni Basel Research Database: Journal article
Identification Number:
Last Modified:08 Feb 2021 10:53
Deposited On:01 Feb 2021 12:19

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