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Title: BTK modulates p53 activity to enhance apoptotic and senescent responses
Authors: Althubiti, Mohammad
Rada, Miran
Samuel, Jesvin
Escorsa, Josep M.
Najeeb, Hishyar
Lee, Koon-Guan
Lam, Kong-Peng
Jones, George D. D.
Barlev, Nickolai
Macip, Salvador
First Published: 26-Jul-2016
Publisher: American Association for Cancer Research
Citation: Cancer Research, 2016, 76 (18), pp. 5405-5414
Abstract: p53 is a tumor suppressor that prevents the emergence of transformed cells by inducing apoptosis or senescence, among other responses. Its functions are regulated tightly by posttranslational modifications. Here we show that Bruton's tyrosine kinase (BTK) is a novel modulator of p53. We found that BTK is induced in response to DNA damage and p53 activation. BTK induction leads to p53 phosphorylation, which constitutes a positive feedback loop that increases p53 protein levels and enhances the transactivation of its target genes in response to stress. Inhibiting BTK reduced both p53-dependent senescence and apoptosis. Further, BTK expression also upregulated DNA damage signals and apoptosis. We conclude that despite being involved in oncogenic signals in blood malignancies, BTK has antineoplastic properties in other contexts, such as the enhancement of p53's tumor suppressor responses. Along with evidence that BTK expression correlates with good prognosis in some epithelial tumors, our findings may encourage a reevaluation of the clinical uses of BTK inhibitors in cancer therapy.
DOI Link: 10.1158/0008-5472.CAN-16-0690
ISSN: 0008-5472
eISSN: 1538-7445
Version: Post-print
Status: Peer-reviewed
Type: Journal Article
Rights: Copyright © American Association for Cancer Research, 2016. This version of the article is distributed under the terms of the Creative Commons Attribution-Non Commercial-No Derivatives License ( ), which permits use and distribution in any medium, provided the original work is properly cited, the use is non-commercial and no modifications or adaptations are made.
Appears in Collections:Published Articles, Dept. of Molecular and Cell Biology

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