Potent and selective caspase-2 inhibitor prevents MDM-2 cleavage in reversine-treated colon cancer cells. View Full Text


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Article Info

DATE

2019-04-11

AUTHORS

Marcin Poreba, Wioletta Rut, Katarzyna Groborz, Scott J Snipas, Guy S Salvesen, Marcin Drag

ABSTRACT

Most caspases can be positioned unambiguously within the regulated cell death networks of apoptosis and pyroptosis, but the role of caspase-2, a highly conserved protease within the family, remains enigmatic. This is mainly due to lack of selective chemical and biochemical tools for the investigation of this protease. In this study, we used our hybrid combinatorial substrate library (HyCoSuL) approach to broadly profile caspase-2 substrate specificity using peptide scanning libraries. This screen uncovered previously unknown caspase-2 peptidyl substrate preferences, which were further used to develop caspase-2 selective fluorogenic substrates and covalent, irreversible AOMK inhibitors. Finally, we used the champion inhibitor (NH-23-C2) in reversine-treated HCT-116 colon cancer cells to selectively block caspase-2 activity and caspase-2-mediated MDM-2 cleavage. In addition, we showed that NH-23-C2 does not block caspase-3 or caspase-8, which makes it a powerful chemical tool to dissect the true role of caspase-2 in various biological setups. More... »

References to SciGraph publications

  • 2000-11. Deficiency in caspase-9 or caspase-3 induces compensatory caspase activation in NATURE MEDICINE
  • 2018-05-10. Caspase selective reagents for diagnosing apoptotic mechanisms in CELL DEATH & DIFFERENTIATION
  • 2008-02. Overlapping cleavage motif selectivity of caspases: implications for analysis of apoptotic pathways in CELL DEATH & DIFFERENTIATION
  • 2016-02. Caspase-2 promotes obesity, the metabolic syndrome and nonalcoholic fatty liver disease in CELL DEATH & DISEASE
  • 2009-02. The enigma of caspase-2: the laymen's view in CELL DEATH & DIFFERENTIATION
  • 2002-03. Tumor-cell resistance to death receptor–induced apoptosis through mutational inactivation of the proapoptotic Bcl-2 homolog Bax in NATURE MEDICINE
  • 2004-05. Mitotic catastrophe constitutes a special case of apoptosis whose suppression entails aneuploidy in ONCOGENE
  • 2012-01. Caspase-2: the orphan caspase in CELL DEATH & DIFFERENTIATION
  • 2014-09. Unnatural amino acids increase sensitivity and provide for the design of highly selective caspase substrates in CELL DEATH & DIFFERENTIATION
  • 2006-01. In situ trapping of activated initiator caspases reveals a role for caspase-2 in heat shock-induced apoptosis in NATURE CELL BIOLOGY
  • 2015-10. Cleavage of GSDMD by inflammatory caspases determines pyroptotic cell death in NATURE
  • 2012-10. PIDDosome-independent tumor suppression by Caspase-2 in CELL DEATH & DIFFERENTIATION
  • 2009-12. Caspase 2 in apoptosis, the DNA damage response and tumour suppression: enigma no more? in NATURE REVIEWS CANCER
  • 2017-09-21. Synthesis of a HyCoSuL peptide substrate library to dissect protease substrate specificity in NATURE PROTOCOLS
  • 2014. Positional Scanning Substrate Combinatorial Library (PS-SCL) Approach to Define Caspase Substrate Specificity in CASPASES,PARACASPASES, AND METACASPASES
  • 2015-04. Old, new and emerging functions of caspases in CELL DEATH & DIFFERENTIATION
  • 2007-02. Broad-spectrum caspase inhibitors: from myth to reality? in CELL DEATH & DIFFERENTIATION
  • 2012-08. Caspase-2 deficiency promotes aberrant DNA-damage response and genetic instability in CELL DEATH & DIFFERENTIATION
  • 2011-06. Ocular neuroprotection by siRNA targeting caspase-2 in CELL DEATH & DISEASE
  • Identifiers

    URI

    http://scigraph.springernature.com/pub.10.1038/s41418-019-0329-2

    DOI

    http://dx.doi.org/10.1038/s41418-019-0329-2

    DIMENSIONS

    https://app.dimensions.ai/details/publication/pub.1113378372

    PUBMED

    https://www.ncbi.nlm.nih.gov/pubmed/30976094


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    N-Triples is a line-based linked data format ideal for batch operations.

    curl -H 'Accept: application/n-triples' 'https://scigraph.springernature.com/pub.10.1038/s41418-019-0329-2'

    Turtle is a human-readable linked data format.

    curl -H 'Accept: text/turtle' 'https://scigraph.springernature.com/pub.10.1038/s41418-019-0329-2'

    RDF/XML is a standard XML format for linked data.

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