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

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

doi:10.1016/j.ccr.2008.05.016

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

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

Biosciences

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

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).

Original language	English
Pages (from-to)	23-35
Number of pages	13
Journal	Cancer Cell
Volume	14
Issue number	1
DOIs	https://doi.org/10.1016/j.ccr.2008.05.016
Publication status	Published - 8 Jul 2008

Keywords

Angiogenesis Inhibitors/pharmacology
Animals
Apoptosis/drug effects
Blood Vessels/drug effects
Boronic Acids/pharmacology
Bortezomib
Cell Cycle/drug effects
Cell Proliferation/drug effects
Cyclin-Dependent Kinase Inhibitor p27
Cysteine Proteinase Inhibitors/pharmacology
Dose-Response Relationship, Drug
HCT116 Cells
HeLa Cells
Humans
Intracellular Signaling Peptides and Proteins/metabolism
Mice
Mice, Nude
Necrosis
Neoplasms/blood supply
Neovascularization, Pathologic/enzymology
Peptides, Cyclic/pharmacology
Proteasome Endopeptidase Complex/genetics
Proteasome Inhibitors
Protein Processing, Post-Translational/drug effects
Pyrazines/pharmacology
RNA Interference
RNA, Small Interfering/metabolism
Time Factors
Transfection
Up-Regulation
Xenograft Model Antitumor Assays

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1016/j.ccr.2008.05.016

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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 p27(kip1) 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

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

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).",

keywords = "Angiogenesis Inhibitors/pharmacology, Animals, Apoptosis/drug effects, Blood Vessels/drug effects, Boronic Acids/pharmacology, Bortezomib, Cell Cycle/drug effects, Cell Proliferation/drug effects, Cyclin-Dependent Kinase Inhibitor p27, Cysteine Proteinase Inhibitors/pharmacology, Dose-Response Relationship, Drug, HCT116 Cells, HeLa Cells, Humans, Intracellular Signaling Peptides and Proteins/metabolism, Mice, Mice, Nude, Necrosis, Neoplasms/blood supply, Neovascularization, Pathologic/enzymology, Peptides, Cyclic/pharmacology, Proteasome Endopeptidase Complex/genetics, Proteasome Inhibitors, Protein Processing, Post-Translational/drug effects, Pyrazines/pharmacology, RNA Interference, RNA, Small Interfering/metabolism, Time Factors, Transfection, Up-Regulation, Xenograft Model Antitumor Assays",

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}",

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month = jul,

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doi = "10.1016/j.ccr.2008.05.016",

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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 p27(kip1) 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

TY - JOUR

T1 - Argyrin a reveals a critical role for the tumor suppressor protein p27(kip1) 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

PY - 2008/7/8

Y1 - 2008/7/8

N2 - 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).

AB - 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).

KW - Angiogenesis Inhibitors/pharmacology

KW - Animals

KW - Apoptosis/drug effects

KW - Blood Vessels/drug effects

KW - Boronic Acids/pharmacology

KW - Bortezomib

KW - Cell Cycle/drug effects

KW - Cell Proliferation/drug effects

KW - Cyclin-Dependent Kinase Inhibitor p27

KW - Cysteine Proteinase Inhibitors/pharmacology

KW - Dose-Response Relationship, Drug

KW - HCT116 Cells

KW - HeLa Cells

KW - Humans

KW - Intracellular Signaling Peptides and Proteins/metabolism

KW - Mice

KW - Mice, Nude

KW - Necrosis

KW - Neoplasms/blood supply

KW - Neovascularization, Pathologic/enzymology

KW - Peptides, Cyclic/pharmacology

KW - Proteasome Endopeptidase Complex/genetics

KW - Proteasome Inhibitors

KW - Protein Processing, Post-Translational/drug effects

KW - Pyrazines/pharmacology

KW - RNA Interference

KW - RNA, Small Interfering/metabolism

KW - Time Factors

KW - Transfection

KW - Up-Regulation

KW - Xenograft Model Antitumor Assays

U2 - 10.1016/j.ccr.2008.05.016

DO - 10.1016/j.ccr.2008.05.016

M3 - Article

C2 - 18598941

SN - 1535-6108

VL - 14

SP - 23

EP - 35

JO - Cancer Cell

JF - Cancer Cell

IS - 1

ER -

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

Abstract

Keywords

UN SDGs

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