Details
| Originalsprache | Englisch |
|---|---|
| Seiten (von - bis) | 23-35 |
| Seitenumfang | 13 |
| Fachzeitschrift | CANCER CELL |
| Jahrgang | 14 |
| Ausgabenummer | 1 |
| Publikationsstatus | Veröffentlicht - 8 Juli 2008 |
| Extern publiziert | Ja |
Abstract
A reduction 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.
ASJC Scopus Sachgebiete
- Medizin (insg.)
- Onkologie
- Biochemie, Genetik und Molekularbiologie (insg.)
- Zellbiologie
- Biochemie, Genetik und Molekularbiologie (insg.)
- Krebsforschung
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in: CANCER CELL, Jahrgang 14, Nr. 1, 08.07.2008, S. 23-35.
Publikation: Beitrag in Fachzeitschrift › Artikel › Forschung › Peer-Review
}
TY - JOUR
T1 - Argyrin A Reveals a Critical Role for the Tumor Suppressor Protein p27kip1 in Mediating Antitumor Activities in Response to Proteasome Inhibition
AU - Nickeleit, Irina
AU - Zender, Steffen
AU - Sasse, Florenz
AU - Geffers, Robert
AU - Brandes, Gudrun
AU - Sörensen, Inga
AU - Steinmetz, Heinrich
AU - Kubicka, Stefan
AU - Carlomagno, Teresa
AU - Menche, Dirk
AU - Gütgemann, Ines
AU - Buer, Jan
AU - Gossler, Achim
AU - Manns, Michael P.
AU - Kalesse, Markus
AU - Frank, Ronald
AU - Malek, Nisar P.
N1 - Funding Information: We thank Bettina Hinkelmann and Tanja Töpfer for excellent technical assistance, Maria Höxter for help with FACS analysis, Britta Wieland for supply of cell lines, ChemBioNet for logistical support, H.A. Sundberg Malek for helpful discussions, and Arnaud Besson for p27C-K- MEFs and helpful discussions. This work was supported by grants from the Deutsche Krebshilfe (Max Eder Program) and the Deutsche Forschungsgemeinschaft to N.P.M. and by Bundesministerium für Bildung und Forschung grant 01GR0474 of the German National Genome Research Net (NGFN2) to R.F.
PY - 2008/7/8
Y1 - 2008/7/8
N2 - A reduction 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.
AB - A reduction 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.
KW - CELLCYCLE
KW - CHEMBIO
UR - http://www.scopus.com/inward/record.url?scp=45849099115&partnerID=8YFLogxK
U2 - 10.1016/j.ccr.2008.05.016
DO - 10.1016/j.ccr.2008.05.016
M3 - Article
C2 - 18598941
AN - SCOPUS:45849099115
VL - 14
SP - 23
EP - 35
JO - CANCER CELL
JF - CANCER CELL
SN - 1535-6108
IS - 1
ER -