Stathmin Inhibition Enhances Okadaic Acid-induced Mitotic Arrest

Stathmin is a microtubule-destabilizing phosphoprotein that plays a critical role in the regulation of mitosis. The microtubule-depolymerizing activity of stathmin is lost upon phosphorylation in mitosis. Although the role of phosphorylation of stathmin by p34 cdc2 kinase in the assembly of the mitotic spindle is well established, the role of dephosphorylation of stathmin in mitosis is unknown. In this study, we tested the hypothesis that dephosphorylation of stathmin may be critically important for the depolymerization of the mitotic spindle and the exit from mitosis. We compared the effects of okadaic acid, a specific inhibitor of serine/threonine protein phosphatases, on different parameters of mitotic progression in the presence or absence of stathmin deficiency. Because okadaic acid prevents dephosphorylation of stathmin and results in accumulation of the inactive phosphorylated form, exposure to okadaic acid would be expected to have a more profound effect on mitosis in the presence of relative stathmin deficiency. We found that inhibition of stathmin expression results in increased sensitivity to the antimitotic effects of okadaic acid. This was reflected by increased growth inhibition associated with mitotic arrest. A vast majority of the stathmin-inhibited cells were found to be arrested in late metaphase/anaphase and had severe mitotic spindle abnormalities. Exposure to okadaic acid also resulted in a bigger ratio of polymerized/unpolymerized tubulin in stathmin-inhibited cells relative to control cells. Because the only difference between the control and the stathmin-inhibited cells is the deficiency of stathmin in the latter, the increased susceptibility of the stathmin-inhibited cells to okadaic acid-induced mitotic arrest implies a role for stathmin in the later stages of mitosis.

• Publication year

  2001

• Venue

  Journal of Biological Chemistry

• Publication date

  2001-08-17

• Fields of study

  Biology, Medicine

• Identifiers
  DOI 10.1074/JBC.M011654200PMID 11418586
• External record

  Open on Semantic Scholar

• Source metadata

  Semantic Scholar, PubMed

• No claims are published for this paper.

• No concepts are published for this paper.

• Decreasing oncoprotein 18/stathmin levels reduces microtubule catastrophes and increases microtubule polymer in vivo.

  1999cited by this paper
• Regulation of Microtubule Dynamics by Extracellular Signals: cAMP-dependent Protein Kinase Switches Off the Activity of Oncoprotein 18 in Intact Cells

  1998cited by this paper
• Role for protein phosphatases in the cell-cycle-regulated phosphorylation of stathmin.

  1998cited by this paper
• The Microtubule-destabilizing Activity of Metablastin (p19) Is Controlled by Phosphorylation*

  1997cited by this paper
• Regulation of microtubule dynamics by Ca2+/calmodulin-dependent kinase IV/Gr-dependent phosphorylation of oncoprotein 18

  1997cited by this paper
• Oncoprotein 18 is a phosphorylation‐responsive regulator of microtubule dynamics.

  1996cited by this paper
• Identification of a protein that interacts with tubulin dimers and increases the catastrophe rate of microtubules.

  1996cited by this paper
• Antisense RNA inhibition of phosphoprotein p18 expression abrogates the transformed phenotype of leukemic cells.

  1996cited by this paper
• G2/M Transition Requires Multisite Phosphorylation of Oncoprotein 18 by Two Distinct Protein Kinase Systems (*)

  1995cited by this paper
• Regulation of phosphoprotein p18 in leukemic cells. Cell cycle regulated phosphorylation by p34cdc2 kinase.

  1994cited by this paper
• Serine 25 of oncoprotein 18 is a major cytosolic target for the mitogen-activated protein kinase.

  1993cited by this paper
• Multiple phosphorylation of stathmin. Identification of four sites phosphorylated in intact cells and in vitro by cyclic AMP-dependent protein kinase and p34cdc2.

  1993cited by this paper
• Okadaic acid inhibits sister chromatid separation in mammalian cells.

  1992cited by this paper
• Okadaic acid--a valuable new tool for the study of signal transduction and cell cycle regulation?

  1992cited by this paper
• Okadaic acid inhibits a protein phosphatase activity involved in formation of the mitotic spindle of GH4 rat pituitary cells

  1992cited by this paper
• Inhibition of mitosis by okadaic acid: possible involvement of a protein phosphatase 2A in the transition from metaphase to anaphase.

  1992cited by this paper
• Mitotic arrest and enhanced nuclear protein phosphorylation in human leukemia K562 cells by okadaic acid, a potent protein phosphatase inhibitor and tumor promoter.

  1991cited by this paper
• Resistance to antimitotic drugs in Chinese hamster ovary cells correlates with changes in the level of polymerized tubulin.

  1991cited by this paper
• Use of okadaic acid to inhibit protein phosphatases in intact cells.

  1991cited by this paper
• Simultaneous quantification of c-myc oncoprotein, total cellular protein, and DNA content using multiparameter flow cytometry.

  1991cited by this paper
• Alteration of microtubule physiology in hepatocytes by insulin

  1989cited by this paper
• Involvement of protein phosphatases 1 and 2A in the control of M phase- promoting factor activity in starfish

  1989cited by this paper
• The bimG gene of Aspergillus nidulans, required for completion of anaphase, encodes a homolog of mammalian phosphoprotein phosphatase 1.

  1989cited by this paper
• The fission yeast dis2+ gene required for chromosome disjoining encodes one of two putative type 1 protein phosphatases.

  1989cited by this paper
• Macrophage Microtubules: An Optimized Method for the Assay of Tubulin Concentration and State of Polymerization in Macrophages

  1984cited by this paper
• Quantitative biochemical analysis of microtubule content in normal and transformed 3T3 cells

  1979cited by this paper

• The knockdown of stathmin with si-RNA inhibits invasion of mesothelioma.

  2024cites this paper
• STMN1 is highly expressed and contributes to clonogenicity in acute promyelocytic leukemia cells

  2021cites this paper
• Synthetic cyclopenta[b]indoles exhibit antineoplastic activity by targeting microtubule dynamics in acute myeloid leukemia cells.

  2021cites this paper
• Stathmin expression associates with vascular and immune responses in aggressive breast cancer subgroups

  2020cites this paper
• Stathmin/Op18 depletion induces genomic instability and leads to premature senescence in human normal fibroblasts

  2018cites this paper
• Stathmin Is Required for Normal Mouse Mammary Gland Development and Δ16HER2-Driven Tumorigenesis.

  2018cites this paper
• Depletion Induces Genomic Instability and Leads to Premature Senescence in Human Normal Fibroblasts † Running head : stathmin depletion induces senescence in IMR-90

  2017cites this paper
• Single cell analysis uncovers clonal heterogeneity inthe adult exocrine pancreas

  2017cites this paper
• Standardized Cannabis sativa extract attenuates tau and stathmin gene expression in the melanoma cell line

  2017cites this paper
• Microtubule‐Binding Proteins as Promising Biomarkers of Paclitaxel Sensitivity in Cancer Chemotherapy

  2016cites this paper
• Elevated STMN1 Expression Correlates with Poor Prognosis in Patients with Pancreatic Ductal Adenocarcinoma

  2015cites this paper
• Stathmin destabilizing microtubule dynamics promotes malignant potential in cancer cells by epithelial-mesenchymal transition.

  2014cites this paper
• Stathmin is key in reversion of doxorubicin resistance by arsenic trioxide in osteosarcoma cells.

  2014cites this paper
• Cell cycle inhibition therapy that targets stathmin in in vitro and in vivo models of breast cancer

  2013cites this paper
• New Paradigms in Microtubule-Mediated Endocrine Signaling in Prostate Cancer

  2013cites this paper
• PDEF downregulates stathmin expression in prostate cancer.

  2012cites this paper
• MiR-101 Is Involved in Human Breast Carcinogenesis by Targeting Stathmin1

  2012cites this paper
• Novel therapeutic potential in targeting microtubules by nanoparticle albumin-bound paclitaxel in hepatocellular carcinoma.

  2011cites this paper
• CDK1-mediated Phosphorylation of Abi1 Attenuates Bcr-Abl-induced F-actin Assembly and Tyrosine Phosphorylation of WAVE Complex during Mitosis*

  2011cites this paper
• Stathmin: a protein with many tasks. New biomarker and potential target in cancer

  2011cites this paper
• Overexpression of stathmin1 in the diffuse type of gastric cancer and its roles in proliferation and migration of gastric cancer cells

  2010cites this paper
• Hedgehog signaling regulates proliferation of prostate cancer cells via stathmin1

  2010cites this paper
• Stathmin, a microtubule regulatory protein, is associated with hypoxia-inducible factor-1alpha levels in human endometrial and endothelial cells.

  2009cites this paper
• Dose response evaluation of gene expression profiles in the skin of K6/ODC mice exposed to sodium arsenite.

  2008cites this paper
• Expression of stathmin, a microtubule regulatory protein, is associated with the migration and differentiation of cultured early trophoblasts.

  2008cites this paper
• Stathmin 1: a novel therapeutic target for anticancer activity

  2008cites this paper
• Identification of stathmin 1 expression induced by Epstein–Barr virus in human B lymphocytes

  2007influential citation
• Synergistic Antiangiogenic Effects of Stathmin Inhibition and Taxol Exposure

  2007cites this paper
• Proteome and cytoskeleton responses in osteosarcoma cells with reduced OXPHOS activity

  2007cites this paper
• Microtubule-Associated Proteins as Targets in Cancer Chemotherapy

  2007cites this paper
• Somatostatin effects on the proteome of the LNCaP cell-line.

  2007cites this paper
• Forced Expression of Survivin-2B Abrogates Mitotic Cells and Induces Mitochondria-dependent Apoptosis by Blockade of Tubulin Polymerization and Modulation of Bcl-2, Bax, and Survivin*

  2007cites this paper
• Inhibiting Proliferation and Enhancing Chemosensitivity to Taxanes in Osteosarcoma Cells by RNA Interference-Mediated Downregulation of Stathmin Expression

  2007cites this paper
• NuSAP is degraded by APC/C-Cdh1 and its overexpression results in mitotic arrest dependent of its microtubules' affinity.

  2007cites this paper
• Reversal of Stathmin-Mediated Resistance to Paclitaxel and Vinblastine in Human Breast Carcinoma Cells

  2007cites this paper
• Structure and thermodynamics of the tubulin-stathmin interaction.

  2007cites this paper
• Molecular and cell phenotype changes in mitochondrial diseases

  2007cites this paper
• Homeodomain Transcription Factor Phox2a, via Cyclic AMP-Mediated Activation, Induces p27Kip1 Transcription, Coordinating Neural Progenitor Cell Cycle Exit and Differentiation

  2006cites this paper
• Therapeutic interactions between stathmin inhibition and chemotherapeutic agents in prostate cancer

  2006cites this paper
• Proteomic analysis of acute promyelocytic leukemia: PML‐RARα leads to decreased phosphorylation of OP18 at serine 63

  2006cites this paper
• Stathmin Prevents the Transition from a Normal to an Endomitotic Cell Cycle during Megakaryocytic Differentiation

  2005cites this paper
• Stathmin expression modulates migratory properties of GN-11 neurons in vitro.

  2005cites this paper
• Distinct and sequential upregulation of genes regulating cell growth and cell cycle progression during hepatic ischemia-reperfusion injury.

  2005cites this paper
• Targeting stathmin in prostate cancer

  2005cites this paper
• 6 , 6-Pentachlorobiphenyl Induces Mitotic Arrest and p 53 Activation

  2004cites this paper
• The role of stathmin in the regulation of the cell cycle

  2004cites this paper
• 2,2',4,6,6'-Pentachlorobiphenyl induces mitotic arrest and p53 activation.

  2004cites this paper
• JWA protein binds to a-tubulin in PC12 cells

  2004cites this paper
• GnRH : Gonadotropin-releasing hormone HGF / SF : Hepatocyte Growth Factor / Scatter Factor MT : microtubule PAF : paraformaldehyde PBS : phosphate-buffered saline SFM : Serum Free Medium

  2004cites this paper
• JWA protein binds to α-tubulin in PC 12 cells

  2004cites this paper
• 2,2 (cid:1) ,4,6,6 (cid:1) -Pentachlorobiphenyl Induces Mitotic Arrest and p53 Activation

  2004cites this paper
• Genomic Expression Discovery Predicts Pathways and Opposing Functions behind Phenotypes*

  2003cites this paper
• Altered levels and regulation of stathmin in paclitaxel-resistant ovarian cancer cells

  2003cites this paper
• The Effect of Stathmin Phosphorylation on Microtubule Assembly Depends on Tubulin Critical Concentration* 210

  2002cites this paper
• Role of stathmin in the regulation of the mitotic spindle: potential applications in cancer therapy.

  2002cites this paper
• Identification of novel targets for cancer therapy using expression proteomics

  2002cites this paper