Argyrin A Reveals a Critical Role for the Tumor Suppressor Protein p27kip1 in Mediating Antitumor Activities in Response to Proteasome Inhibition

Research output: Contribution to journal › Article › Research › peer review

Authors

  • 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

External Research Organisations

  • Hannover Medical School (MHH)
  • Helmholtz Centre for Infection Research (HZI)
  • Max Planck Institute for Biophysical Chemistry (Karl Friedrich Bonhoeffer Institute)
  • University of Bonn
View graph of relations

Details

Original languageEnglish
Pages (from-to)23-35
Number of pages13
JournalCANCER CELL
Volume14
Issue number1
Publication statusPublished - 8 Jul 2008
Externally publishedYes

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.

Keywords

    CELLCYCLE, CHEMBIO

ASJC Scopus subject areas

Sustainable Development Goals

Cite this

Argyrin A Reveals a Critical Role for the Tumor Suppressor Protein p27kip1 in Mediating Antitumor Activities in Response to Proteasome Inhibition. / Nickeleit, Irina; Zender, Steffen; Sasse, Florenz et al.
In: CANCER CELL, Vol. 14, No. 1, 08.07.2008, p. 23-35.

Research output: Contribution to journal › Article › Research › peer review

Nickeleit, I, Zender, S, Sasse, F, Geffers, R, Brandes, G, Sörensen, I, Steinmetz, H, Kubicka, S, Carlomagno, T, Menche, D, Gütgemann, I, Buer, J, Gossler, A, Manns, MP, Kalesse, M, Frank, R & Malek, NP 2008, 'Argyrin A Reveals a Critical Role for the Tumor Suppressor Protein p27kip1 in Mediating Antitumor Activities in Response to Proteasome Inhibition', CANCER CELL, vol. 14, no. 1, pp. 23-35. https://doi.org/10.1016/j.ccr.2008.05.016
Nickeleit, I., Zender, S., Sasse, F., Geffers, R., Brandes, G., Sörensen, I., Steinmetz, H., Kubicka, S., Carlomagno, T., Menche, D., Gütgemann, I., Buer, J., Gossler, A., Manns, M. P., Kalesse, M., Frank, R., & Malek, N. P. (2008). Argyrin A Reveals a Critical Role for the Tumor Suppressor Protein p27kip1 in Mediating Antitumor Activities in Response to Proteasome Inhibition. CANCER CELL, 14(1), 23-35. https://doi.org/10.1016/j.ccr.2008.05.016
Nickeleit I, Zender S, Sasse F, Geffers R, Brandes G, Sörensen I et al. Argyrin A Reveals a Critical Role for the Tumor Suppressor Protein p27kip1 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
Nickeleit, Irina ; Zender, Steffen ; Sasse, Florenz et al. / Argyrin A Reveals a Critical Role for the Tumor Suppressor Protein p27kip1 in Mediating Antitumor Activities in Response to Proteasome Inhibition. In: CANCER CELL. 2008 ; Vol. 14, No. 1. pp. 23-35.
Download
@article{b6d3c46d257b4e19b4e42dec8e88856f,
title = "Argyrin A Reveals a Critical Role for the Tumor Suppressor Protein p27kip1 in Mediating Antitumor Activities in Response to Proteasome Inhibition",
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.",
keywords = "CELLCYCLE, CHEMBIO",
author = "Irina Nickeleit and Steffen Zender and Florenz Sasse and Robert Geffers and Gudrun Brandes and Inga S{\"o}rensen and Heinrich Steinmetz and Stefan Kubicka and Teresa Carlomagno and Dirk Menche and Ines G{\"u}tgemann and Jan Buer and Achim Gossler and Manns, {Michael P.} and Markus Kalesse and Ronald Frank and Malek, {Nisar P.}",
note = "Funding Information: We thank Bettina Hinkelmann and Tanja T{\"o}pfer for excellent technical assistance, Maria H{\"o}xter 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 f{\"u}r Bildung und Forschung grant 01GR0474 of the German National Genome Research Net (NGFN2) to R.F. ",
year = "2008",
month = jul,
day = "8",
doi = "10.1016/j.ccr.2008.05.016",
language = "English",
volume = "14",
pages = "23--35",
journal = "CANCER CELL",
issn = "1535-6108",
publisher = "Cell Press",
number = "1",

}

Download

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 -

By the same author(s)

  1. Total Synthesis of Acanthodoral Using a Rearrangement Strategy

    Research output: Contribution to journal › Article › Research › peer review

  2. Development of the Synthesis of Desepoxy-Tedanolide C

    Research output: Contribution to journal › Article › Research › peer review

  3. Stereoselective Synthesis of Allylic Alcohols via Substrate Control on Asymmetric Lithiation

    Research output: Contribution to journal › Article › Research › peer review

  4. Stereoselective Construction of β-chiral Homoallyl Functionalities by Substrate- and Reagent-Controlled Iterative 1,2-Metallate Rearrangements

    Research output: Contribution to journal › Article › Research › peer review

  5. 1,2-Metallate Rearrangement as a Toolbox for the Synthesis of Allylic Alcohols

    Research output: Contribution to journal › Article › Research › peer review