Note to users. If you're seeing this message, it means that your browser cannot find this page's style/presentation instructions -- or possibly that you are using a browser that does not support current Web standards. Find out more about why this message is appearing, and what you can do to make your experience of our site the best it can be.
Subscribe

Sci. Signal., 29 March 2011
Vol. 4, Issue 166, p. ra19
[DOI: 10.1126/scisignal.2001556]

RESEARCH ARTICLES

c-MYC Suppresses BIN1 to Release Poly(ADP-Ribose) Polymerase 1: A Mechanism by Which Cancer Cells Acquire Cisplatin Resistance

Slovénie Pyndiah1,2*{dagger}, Satoshi Tanida1,2*{ddagger}, Kazi M. Ahmed3,4*||, Erica K. Cassimere1,2,3,4, Chungyoul Choe1,2, and Daitoku Sakamuro1,2,3,4#

1 Molecular Signaling Program, Stanley S. Scott Cancer Center, Louisiana State University Health Sciences Center, New Orleans, LA 70112, USA.
2 Department of Pathology, Louisiana State University Health Sciences Center, New Orleans, LA 70112, USA.
3 Cell Growth and Differentiation Program, Purdue Cancer Center–Walther Cancer Institute, Purdue University, West Lafayette, IN 47907, USA.
4 Department of Medicinal Chemistry and Molecular Pharmacology, Purdue University, West Lafayette, IN 47907, USA.

* These authors contributed equally to this work.

{dagger} Present address: Hôpital St. Louis, Institut de Génétique Moléculaire, Cibles Thérapeutiques, INSERM U940, F-75010 Paris, France.

{ddagger} Present address: Department of Gastroenterology and Metabolism, Nagoya City University Graduate School of Medical Sciences, Nagoya 467, Japan.

|| Present address: Department of Cancer and DNA Damage Responses, Ernest Orlando Lawrence Berkeley National Laboratory, Berkeley, CA 94710, USA.

Present address: Department of Integrative Biology and Pharmacology, University of Texas Health Science Center, Houston, TX 77030, USA.

Abstract: Cancer cells acquire resistance to DNA-damaging therapeutic agents, such as cisplatin, but the genetic mechanisms through which this occurs remain unclear. We show that the c-MYC oncoprotein increases cisplatin resistance by decreasing production of the c-MYC inhibitor BIN1 (bridging integrator 1). The sensitivity of cancer cells to cisplatin depended on BIN1 abundance, regardless of the p53 gene status. BIN1 bound to the automodification domain of and suppressed the catalytic activity of poly(ADP-ribose) polymerase 1 (PARP1, EC 2.4.2.30), an enzyme essential for DNA repair, thereby reducing the stability of the genome. The inhibition of PARP1 activity was sufficient for BIN1 to suppress c-MYC–mediated transactivation, the G2-M transition, and cisplatin resistance. Conversely, overexpressed c-MYC repressed BIN1 expression by blocking its activation by the MYC-interacting zinc finger transcription factor 1 (MIZ1) and thereby released PARP1 activity. Thus, a c-MYC–mediated positive feedback loop may contribute to cancer cell resistance to cisplatin.

# To whom correspondence should be addressed. E-mail: dsakam{at}lsuhsc.edu

Citation: S. Pyndiah, S. Tanida, K. M. Ahmed, E. K. Cassimere, C. Choe, D. Sakamuro, c-MYC Suppresses BIN1 to Release Poly(ADP-Ribose) Polymerase 1: A Mechanism by Which Cancer Cells Acquire Cisplatin Resistance. Sci. Signal. 4, ra19 (2011).

Read the Full Text

THIS ARTICLE HAS BEEN CITED BY OTHER ARTICLES:
Poly(ADP-ribose) polymerase 1 regulates nuclear reprogramming and promotes iPSC generation without c-Myc.
S.-H. Chiou, B.-H. Jiang, Y.-L. Yu, S.-J. Chou, P.-H. Tsai, W.-C. Chang, L.-K. Chen, L.-H. Chen, Y. Chien, and G.-Y. Chiou (2013)
J. Exp. Med. 210, 85-98
   Abstract »    Full Text »    PDF »
MYC, PARP1, and Chemoresistance: BIN There, Done That?.
S. Ganesan (2011)
Science Signaling 4, pe15
   Abstract »    Full Text »    PDF »

To Advertise     Find Products

Science Signaling. ISSN 1937-9145 (online), 1945-0877 (print). Pre-2008: Science's STKE. ISSN 1525-8882