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ABSTRACT We previously identified Caliban (Clbn) as the _Drosophila_ homolog of human Serologically defined colon cancer antigen 1 gene and demonstrated that it could function as a tumor

suppressor in human non-small-cell lung cancer (NSCLC) cells, although its mode of action was unknown. Herein, we identify roles for Clbn in DNA damage response. We generate _clbn_ knockout

flies using homologous recombination and demonstrate that they have a heightened sensitivity to irradiation. We show that normal Clbn function facilitates both p53-dependent and -independent

DNA damage-induced apoptosis. Clbn coordinates different apoptosis pathways, showing a two-stage upregulation following DNA damage. Clbn has proapoptotic functions, working with both

caspase and the proapoptotic gene Hid. Finally, ecotopic expression of _clbn_+ in NSCLC cells suppresses tumor formation in athymic nude mice. We conclude that Caliban is a regulator of DNA

damage-induced apoptosis, functioning as a tumor suppressor in both p53-dependent and -independent pathways. Access through your institution Buy or subscribe This is a preview of

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TP53 AND ENDOD1 Article Open access 23 May 2022 COORDINATION BETWEEN CELL PROLIFERATION AND APOPTOSIS AFTER DNA DAMAGE IN _DROSOPHILA_ Article Open access 25 November 2021 THE P53-CASPASE-2

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_Drosophila_ ventral head. _Dev Biol_ 2006; 296: 329–339. Article  CAS  Google Scholar  Download references ACKNOWLEDGEMENTS We thank Drs Hermann Steller, Laura Johnston and Tin Tin Su; the

Bloomington Stock Center for fly stocks; Dr Dong Han at National Center for Nanoscience and Technology for help with the scanning electron microscope; and the members of the Bi laboratory

for advice and discussions. We also thank Dr Mark Mortin for generating the knockout _clbn_ flies and for critically reading this manuscript. We are grateful for comments on this manuscript

from Tehyen Chu and Brent McCright. This work was supported by grants from National Basic Research Program of China (973 Program grant no. 2010CB934004), National Natural Science Foundation

of China (grant no. 30871388) and CAS Knowledge Innovation Program to XB and by the Food and Drug Administration, Center for Biologics Evaluation and Research. AUTHOR INFORMATION Author

notes * Y Wang and Z Wang: These authors contributed equally to this work. AUTHORS AND AFFILIATIONS * CAS Key Laboratory for Biological Effects of Nanomaterials and Nanosafety, Institute of

High Energy Physics, Chinese Academy of Sciences, Beijing, China Y Wang, Z Wang, Q Yuan & X Bi * Cancer Center, Institute of Cancer Stem Cell, Dalian Medical University, Dalian, China Z

Wang & X Bi * Division of Cellular and Gene Therapies, Center for Biologics Evaluation and Research, Food and Drug Administration, Bethesda, MD, USA, B H Joshi, R K Puri, B Stultz & 

D A Hursh * State Key Laboratory of Brain and Cognitive Sciences, Institute of Biophysics, Chinese Academy of Sciences, Beijing, China Y Bai & Z Yuan * Department of Radiation Toxicology

and Oncology, Beijing Institute of Radiation Medicine, Beijing, China P Zhou Authors * Y Wang View author publications You can also search for this author inPubMed Google Scholar * Z Wang

View author publications You can also search for this author inPubMed Google Scholar * B H Joshi View author publications You can also search for this author inPubMed Google Scholar * R K

Puri View author publications You can also search for this author inPubMed Google Scholar * B Stultz View author publications You can also search for this author inPubMed Google Scholar * Q

Yuan View author publications You can also search for this author inPubMed Google Scholar * Y Bai View author publications You can also search for this author inPubMed Google Scholar * P

Zhou View author publications You can also search for this author inPubMed Google Scholar * Z Yuan View author publications You can also search for this author inPubMed Google Scholar * D A

Hursh View author publications You can also search for this author inPubMed Google Scholar * X Bi View author publications You can also search for this author inPubMed Google Scholar

CORRESPONDING AUTHOR Correspondence to X Bi. ETHICS DECLARATIONS COMPETING INTERESTS The authors declare no conflict of interest. ADDITIONAL INFORMATION Supplementary Information accompanies

the paper on the Oncogene website SUPPLEMENTARY INFORMATION SUPPLEMENTARY INFORMATION (DOC 2737 KB) RIGHTS AND PERMISSIONS Reprints and permissions ABOUT THIS ARTICLE CITE THIS ARTICLE

Wang, Y., Wang, Z., Joshi, B. _et al._ The tumor suppressor Caliban regulates DNA damage-induced apoptosis through p53-dependent and -independent activity. _Oncogene_ 32, 3857–3866 (2013).

https://doi.org/10.1038/onc.2012.395 Download citation * Received: 03 November 2011 * Revised: 04 June 2012 * Accepted: 20 July 2012 * Published: 10 September 2012 * Issue Date: 15 August

2013 * DOI: https://doi.org/10.1038/onc.2012.395 SHARE THIS ARTICLE Anyone you share the following link with will be able to read this content: Get shareable link Sorry, a shareable link is

not currently available for this article. Copy to clipboard Provided by the Springer Nature SharedIt content-sharing initiative KEYWORDS * Apoptosis * Caliban * p53 * tumor suppressor