Format

Send to

Choose Destination
Cancer Res. 2016 Sep 15;76(18):5405-14. doi: 10.1158/0008-5472.CAN-16-0690. Epub 2016 Jul 26.

BTK Modulates p53 Activity to Enhance Apoptotic and Senescent Responses.

Author information

1
Mechanisms of Cancer and Aging Laboratory, Department of Molecular and Cell Biology, University of Leicester, Leicester, United Kingdom. Cancer Research UK Leicester Centre, Leicester, United Kingdom. Department of Biochemistry, Faculty of Medicine, Umm Al-Qura University, Mecca, Saudi Arabia.
2
Mechanisms of Cancer and Aging Laboratory, Department of Molecular and Cell Biology, University of Leicester, Leicester, United Kingdom. Cancer Research UK Leicester Centre, Leicester, United Kingdom. Department of Biology, School of Science, Faculty of Science and Education Sciences, University of Sulaimani, Sulaimaniyah, Kurdistan Region, Iraq.
3
Mechanisms of Cancer and Aging Laboratory, Department of Molecular and Cell Biology, University of Leicester, Leicester, United Kingdom. Cancer Research UK Leicester Centre, Leicester, United Kingdom.
4
Cancer Research UK Leicester Centre, Leicester, United Kingdom. Department of Cancer Studies, University of Leicester, Leicester, United Kingdom.
5
Bioprocessing Technology Institute, A*STAR, Singapore.
6
Institute of Cytology, RAS, Saint-Petersburg, Russia.
7
Mechanisms of Cancer and Aging Laboratory, Department of Molecular and Cell Biology, University of Leicester, Leicester, United Kingdom. Cancer Research UK Leicester Centre, Leicester, United Kingdom. sm460@le.ac.uk.

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. Cancer Res; 76(18); 5405-14.

PMID:
27630139
DOI:
10.1158/0008-5472.CAN-16-0690
[Indexed for MEDLINE]
Free full text

Supplemental Content

Full text links

Icon for HighWire
Loading ...
Support Center