2. Academic Validation
  3. Argyrin a reveals a critical role for the tumor suppressor protein p27(kip1) in mediating antitumor activities in response to proteasome inhibition

Argyrin a reveals a critical role for the tumor suppressor protein p27(kip1) in mediating antitumor activities in response to proteasome inhibition

  • Cancer Cell. 2008 Jul 8;14(1):23-35. doi: 10.1016/j.ccr.2008.05.016.
Irina Nickeleit 1,  Steffen Zender,  Florenz Sasse,  Robert Geffers,  Gudrun Brandes,  Inga Sörensen,  Heinrich Steinmetz,  Stefan Kubicka,  Teresa Carlomagno,  Dirk Menche,  Ines Gütgemann,  Jan Buer,  Achim Gossler,  Michael P Manns,  Markus Kalesse,  Ronald Frank,  Nisar P Malek
Affiliations

Affiliation

  • 1 Institute for Molecular Biology, Hannover Medical School, 30625 Hannover, Germany.
PMID: 18598941 DOI: 10.1016/j.ccr.2008.05.016
Abstract

A reduction in the cellular levels of the cyclin kinase inhibitor p27(kip1) is frequently found in many human cancers and correlates directly with patient prognosis. In this work, we identify argyrin A, a cyclical peptide derived from the myxobacterium Archangium gephyra, as a potent antitumoral drug. All antitumoral activities of argyrin A depend on the prevention of p27(kip1) destruction, as loss of p27(kip1) expression confers resistance to this compound. We find that argyrin A exerts its effects through a potent inhibition of the Proteasome. By comparing the cellular responses exerted by argyrin A with siRNA-mediated knockdown of proteasomal subunits, we find that the biological effects of Proteasome inhibition per se depend on the expression of p27(kip1).

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