Author/Authors :
V. Nickeleit، نويسنده , , Irina and Zender، نويسنده , , Steffen and Sasse، نويسنده , , Florenz and Geffers، نويسنده , , Robert and Brandes، نويسنده , , Gudrun and Sِrensen، نويسنده , , Inga and Steinmetz، نويسنده , , Heinrich and Kubicka، نويسنده , , Stefan and Carlomagno، نويسنده , , Teresa and Menche، نويسنده , , Dirk and Gütgemann، نويسنده , , Ines and Buer، نويسنده , , Jan and Gossler، نويسنده , , Achim and Manns، نويسنده , , Michael P. and Kalesse، نويسنده , , Markus H Frank، نويسنده , , Ronald and Malek، نويسنده , , Nisar P. Malek، نويسنده ,
Abstract :
Summary
ction in the cellular levels of the cyclin kinase inhibitor p27kip1 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 p27kip1 destruction, as loss of p27kip1 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 p27kip1.
