Stathmin/Op18 is a novel mediator of vinblastine activity

Francois Devred; Philipp O. Tsvetkov; Pascale Barbier; Diane Allegro; Susan Band Horwitz; Alexander A. Makarov; Vincent Peyrot

doi:10.1016/j.febslet.2008.06.035

Stathmin/Op18 is a novel mediator of vinblastine activity

Francois Devred, Philipp O. Tsvetkov, Pascale Barbier, Diane Allegro, Susan Band Horwitz, Alexander A. Makarov, Vincent Peyrot

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

29 Scopus citations

Abstract

Microtubule (MT) dynamic instability is tightly regulated by stabilizing and destabilizing proteins, the latter being exemplified by stathmin/Op18, a protein known to destabilize MTs. Studies in cells have indicated that the level of stathmin expression modifies the cytotoxicity of antimicrotubule drugs, such as vinblastine (VLB). Using isothermal titration calorimetry and analytical ultracentrifugation, we show that VLB increases the affinity of stathmin for tubulin 50-fold (and vice versa). These results are the first biochemical evidence of the direct relationship between stathmin and an antimitotic drug, and reveal a new mechanism of action for VLB. Structured summary: MINT-6603918:tubulin beta (uniprotkb:Q9H4B7), tubulin alpha (uniprotkb:Q71U36) and stathmin (uniprotkb:Q71U36) physically interact (MI:0218) by cosedimentation (MI:0027)MINT-6603930:tubulin alpha (uniprotkb:Q71U36) physically interacts (MI:0218) with tubulin beta (uniprotkb:Q9H4B7) and stathmin (uniprotkb:P16949) by isothermal titration calorimetry (MI:0065).

Original language	English (US)
Pages (from-to)	2484-2488
Number of pages	5
Journal	FEBS Letters
Volume	582
Issue number	17
DOIs	https://doi.org/10.1016/j.febslet.2008.06.035
State	Published - Jul 23 2008
Externally published	Yes

Keywords

Analytical ultracentrifugation
Isothermal titration calorimetry
Microtubule
Stathmin
Tubulin
Vinblastine

ASJC Scopus subject areas

Biophysics
Structural Biology
Biochemistry
Molecular Biology
Genetics
Cell Biology

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10.1016/j.febslet.2008.06.035

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@article{62e0c88424ef42d1ae582be207c2edc5,

title = "Stathmin/Op18 is a novel mediator of vinblastine activity",

abstract = "Microtubule (MT) dynamic instability is tightly regulated by stabilizing and destabilizing proteins, the latter being exemplified by stathmin/Op18, a protein known to destabilize MTs. Studies in cells have indicated that the level of stathmin expression modifies the cytotoxicity of antimicrotubule drugs, such as vinblastine (VLB). Using isothermal titration calorimetry and analytical ultracentrifugation, we show that VLB increases the affinity of stathmin for tubulin 50-fold (and vice versa). These results are the first biochemical evidence of the direct relationship between stathmin and an antimitotic drug, and reveal a new mechanism of action for VLB. Structured summary: MINT-6603918:tubulin beta (uniprotkb:Q9H4B7), tubulin alpha (uniprotkb:Q71U36) and stathmin (uniprotkb:Q71U36) physically interact (MI:0218) by cosedimentation (MI:0027)MINT-6603930:tubulin alpha (uniprotkb:Q71U36) physically interacts (MI:0218) with tubulin beta (uniprotkb:Q9H4B7) and stathmin (uniprotkb:P16949) by isothermal titration calorimetry (MI:0065).",

keywords = "Analytical ultracentrifugation, Isothermal titration calorimetry, Microtubule, Stathmin, Tubulin, Vinblastine",

author = "Francois Devred and Tsvetkov, {Philipp O.} and Pascale Barbier and Diane Allegro and Horwitz, {Susan Band} and Makarov, {Alexander A.} and Vincent Peyrot",

note = "Funding Information: This work was supported by a Grant from the Centre National de la Recherche Scientifique (PICS France-Russie, No. 3841, Programme Proteome), by RFBR Grant 07-04-92165, the Molecular and Cellular Biology Program of the Russian Academy of Sciences, and by USPHS National Cancer Institute Grant CA083185. We thank Robert Michel for protein purifications.",

year = "2008",

month = jul,

day = "23",

doi = "10.1016/j.febslet.2008.06.035",

language = "English (US)",

volume = "582",

pages = "2484--2488",

journal = "FEBS Letters",

issn = "0014-5793",

publisher = "Elsevier",

number = "17",

}

TY - JOUR

T1 - Stathmin/Op18 is a novel mediator of vinblastine activity

AU - Devred, Francois

AU - Tsvetkov, Philipp O.

AU - Barbier, Pascale

AU - Allegro, Diane

AU - Horwitz, Susan Band

AU - Makarov, Alexander A.

AU - Peyrot, Vincent

N1 - Funding Information: This work was supported by a Grant from the Centre National de la Recherche Scientifique (PICS France-Russie, No. 3841, Programme Proteome), by RFBR Grant 07-04-92165, the Molecular and Cellular Biology Program of the Russian Academy of Sciences, and by USPHS National Cancer Institute Grant CA083185. We thank Robert Michel for protein purifications.

PY - 2008/7/23

Y1 - 2008/7/23

N2 - Microtubule (MT) dynamic instability is tightly regulated by stabilizing and destabilizing proteins, the latter being exemplified by stathmin/Op18, a protein known to destabilize MTs. Studies in cells have indicated that the level of stathmin expression modifies the cytotoxicity of antimicrotubule drugs, such as vinblastine (VLB). Using isothermal titration calorimetry and analytical ultracentrifugation, we show that VLB increases the affinity of stathmin for tubulin 50-fold (and vice versa). These results are the first biochemical evidence of the direct relationship between stathmin and an antimitotic drug, and reveal a new mechanism of action for VLB. Structured summary: MINT-6603918:tubulin beta (uniprotkb:Q9H4B7), tubulin alpha (uniprotkb:Q71U36) and stathmin (uniprotkb:Q71U36) physically interact (MI:0218) by cosedimentation (MI:0027)MINT-6603930:tubulin alpha (uniprotkb:Q71U36) physically interacts (MI:0218) with tubulin beta (uniprotkb:Q9H4B7) and stathmin (uniprotkb:P16949) by isothermal titration calorimetry (MI:0065).

AB - Microtubule (MT) dynamic instability is tightly regulated by stabilizing and destabilizing proteins, the latter being exemplified by stathmin/Op18, a protein known to destabilize MTs. Studies in cells have indicated that the level of stathmin expression modifies the cytotoxicity of antimicrotubule drugs, such as vinblastine (VLB). Using isothermal titration calorimetry and analytical ultracentrifugation, we show that VLB increases the affinity of stathmin for tubulin 50-fold (and vice versa). These results are the first biochemical evidence of the direct relationship between stathmin and an antimitotic drug, and reveal a new mechanism of action for VLB. Structured summary: MINT-6603918:tubulin beta (uniprotkb:Q9H4B7), tubulin alpha (uniprotkb:Q71U36) and stathmin (uniprotkb:Q71U36) physically interact (MI:0218) by cosedimentation (MI:0027)MINT-6603930:tubulin alpha (uniprotkb:Q71U36) physically interacts (MI:0218) with tubulin beta (uniprotkb:Q9H4B7) and stathmin (uniprotkb:P16949) by isothermal titration calorimetry (MI:0065).

KW - Analytical ultracentrifugation

KW - Isothermal titration calorimetry

KW - Microtubule

KW - Stathmin

KW - Tubulin

KW - Vinblastine

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U2 - 10.1016/j.febslet.2008.06.035

DO - 10.1016/j.febslet.2008.06.035

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C2 - 18588888

AN - SCOPUS:46749154962

SN - 0014-5793

VL - 582

SP - 2484

EP - 2488

JO - FEBS Letters

JF - FEBS Letters

IS - 17

ER -

Stathmin/Op18 is a novel mediator of vinblastine activity

Abstract

Keywords

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