c-MYC suppresses BIN1 to release poly(ADP-ribose) polymerase 1

A mechanism by which cancer cells acquire cisplatin resistance

Slovénie Pyndiah, Satoshi Tanida, Kazi M. Ahmed, Erica K. Cassimere, Chungyoul Choe, Daitoku Sakamuro

Research output: Contribution to journalArticle

55 Citations (Scopus)

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.

Original languageEnglish (US)
Article numberra19
JournalScience Signaling
Volume4
Issue number166
DOIs
StatePublished - Mar 29 2011

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Poly(ADP-ribose) Polymerases
Cisplatin
Cells
Neoplasms
Genes
DNA Repair Enzymes
Genomic Instability
Oncogene Proteins
DNA
Zinc Fingers
p53 Genes
Transcriptional Activation
Zinc
Catalyst activity
Catalytic Domain
Repair
Transcription Factors
Chemical activation
Poly (ADP-Ribose) Polymerase-1
Feedback

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

Cite this

c-MYC suppresses BIN1 to release poly(ADP-ribose) polymerase 1 : A mechanism by which cancer cells acquire cisplatin resistance. / Pyndiah, Slovénie; Tanida, Satoshi; Ahmed, Kazi M.; Cassimere, Erica K.; Choe, Chungyoul; Sakamuro, Daitoku.

In: Science Signaling, Vol. 4, No. 166, ra19, 29.03.2011.

Research output: Contribution to journalArticle

Pyndiah, Slovénie ; Tanida, Satoshi ; Ahmed, Kazi M. ; Cassimere, Erica K. ; Choe, Chungyoul ; Sakamuro, Daitoku. / c-MYC suppresses BIN1 to release poly(ADP-ribose) polymerase 1 : A mechanism by which cancer cells acquire cisplatin resistance. In: Science Signaling. 2011 ; Vol. 4, No. 166.
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