Argyrin A Reveals a Critical Role for the Tumor Suppressor Protein p27^kip1 in Mediating Antitumor Activities in Response to Proteasome Inhibition

verfasst von

Irina Nickeleit, 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

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.

Externe Organisation(en)

Medizinische Hochschule Hannover (MHH)
Helmholtz-Zentrum für Infektionsforschung GmbH (HZI)
Max-Planck-Institut für biophysikalische Chemie (Karl-Friedrich-Bonhoeffer-Institut)
Rheinische Friedrich-Wilhelms-Universität Bonn

Typ

Artikel

Journal

CANCER CELL

Band

14

Seiten

23-35

Anzahl der Seiten

13

ISSN

1535-6108

Publikationsdatum

08.07.2008

Publikationsstatus

Veröffentlicht

Peer-reviewed

Ja

ASJC Scopus Sachgebiete

Onkologie, Zellbiologie, Krebsforschung

Ziele für nachhaltige Entwicklung

SDG 3 – Gute Gesundheit und Wohlergehen

Elektronische Version(en)

https://doi.org/10.1016/j.ccr.2008.05.016 (Zugang: Offen)