Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “Stathmin”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 109 records · Page 6Linked to original sources
PubMed1998

Luteinizing hormone-releasing hormone-signal transduction and stathmin phosphorylation in the gonadotrope alphaT3-1 cell line.

We have investigated the effects of GnRH (LHRH) and of the protein kinase C (PKC) activator 12-O-tetradecanoylphorbol-13-acetate on stathmin phosphorylation in the gonadotrope alphaT3-1 cell line. Stathmin expression and its phosphorylation were maximal during the exponential phase of cell growth. LHRH stimulated stathmin phosphorylation through a specific receptor in a dose- and time-dependent manner, and TPA induced a similar extensive stathmin phosphorylation. Their effects were inhibited either in PKC-depleted alphaT3-1 cells, or by the PKC inhibitor staurosporine. In the context of the known implication of PKC in LHRH-induced signal transduction, our results show that stathmin phosphorylation is involved in LHRH transduction, either as a result of direct activation of specific PKC isoforms or through a pathway involving kinases downstream to PKC activation.

Animals↗
PubMed2006

Silencing stathmin gene expression by survivin promoter-driven siRNA vector to reverse malignant phenotype of tumor cells.

Stathmin gene overexpression has been shown to play an important role in maintenance of malignant phenotype in tumor cells, and the blocking efficacy and tumor specificity of this target has been concerned in clinical trails. In this report, we designed survivin promoter-driven siRNA eukaryotic expression vector that expressed the small interfering RNA targeting stathmin gene to selectively knock down the stathmin gene expression in two different kinds of tumor cell lines while sparing normal cell lines. The therapeutic potential of this recombinant vector was tested in human cervical cancer Hela cells and osteosarcoma SSOP-9607 cells, and in human umbilical vein endothelial cell line ECV304 cells as control. The siRNA vector- transfected Hela cells and SSOP-9607 cells revealed marked inhibition of stathmin expression and a dramatic growth inhibition comparing with ECV304 cells, parental-vector transfected cells and untransfected cells. Cell cycle analysis of siRNA vector transfected tumor cells by Flow Cytometry showed G(2)/M phase block, while morphologic analysis by TURNEL staining method showed marked increase of apoptosis. Our study indicates that survivin gene promoter-driven stathmin siRNA expression vector may have potential use in tumor gene therapy with targeted tumor gene silencing effect.

Apoptosis↗
PubMed1989

Identification of two distinct isoforms of stathmin and characterization of their respective phosphorylated forms.

Stathmin is a ubiquitous soluble protein (Mr approximately 19,000, pI approximately 6.2-5.5) whose phosphorylation is associated with the intracellular mechanisms involved in the regulations of cell differentiation and functions by extracellular effectors. Its purification from rat brain and the preparation of specific antibodies allowed us to identify a set of immunologically related unphosphorylated (N1, N2) and phosphorylated (P1, P2a, P2b, P3) proteins of decreasing isoelectric points. All these proteins yielded identical silver-stained or 32P-radioactive peptide maps with the protease V8 from Staphylococcus aureus, indicating that they are also structurally related. In vitro phosphorylation with the exogenous catalytic subunit of the cAMP-dependent protein kinase, as well as dephosphorylation with alkaline phosphatase, indicated that P1, P2, and P3 derived from N1 and N2 by progressive phosphorylation. Phosphorylation of individual proteins extracted from semi-preparative two-dimensional polyacrylamide gels demonstrated the existence of two distinct isoforms of stathmin, alpha and beta: N1 and N2 are their respective unphosphorylated forms (alpha O and beta O), whereas proteins P1-P3 could be resolved as at least three increasingly phosphorylated forms of both alpha and beta stathmin (alpha 1, alpha 2, alpha(3) and beta 1, beta 2, beta(3]. In intact pituitary GH4C1 cells, hormones like thyrotropin-releasing hormone and vasoactive intestinal peptide induced a similar conversion from N1 and N2 to P1, P2, and P3. The phosphorylation of both alpha and beta isoforms of stathmin is therefore a physiologically significant response to specific extracellular regulatory agents. In conclusion, stathmin represents a family of at least two distinct protein isoforms, whose respective phosphorylation and expression might play a role in its likely function as an intracellular relay of various converging extracellular signals.

Alkaline Phosphatase↗
PubMed1998

Identification of stathmin as a novel substrate for p38 delta.

p38 mitogen-activated protein kinases (MAPK) are a family of kinases that are activated by cellular stresses and inflammatory cytokines. Although there are many similarities shared by the isoforms of p38 (alpha, beta, gamma, and delta), p38 delta differs from the others in some respects such as inhibitor sensitivity and substrate specificity. Utilizing in a solution kinase assay, we identified a novel p38 delta substrate as stathmin. Stathmin is a cytoplasmic protein that was previously reported to be a substrate of several intracellular signaling kinases and has recently been linked to regulation of microtubule dynamics. p38 delta has significantly higher in vitro phosphorylating activity against stathmin than other p38 isoforms or related MAPKs. In transient expression studies, we found that in addition to different stimuli osmotic stress activates p38 delta to phosphorylate stathmin. The sites of phosphorylation were mapped to Ser-25 and Ser-38, both in vitro and in cells.

Base Sequence↗
PubMed2005

stathmin, a gene enriched in the amygdala, controls both learned and innate fear.

Little is known about the molecular mechanisms of learned and innate fear. We have identified stathmin, an inhibitor of microtubule formation, as highly expressed in the lateral nucleus (LA) of the amygdala as well as in the thalamic and cortical structures that send information to the LA about the conditioned (learned fear) and unconditioned stimuli (innate fear). Whole-cell recordings from amygdala slices that are isolated from stathmin knockout mice show deficits in spike-timing-dependent long-term potentiation (LTP). The knockout mice also exhibit decreased memory in amygdala-dependent fear conditioning and fail to recognize danger in innately aversive environments. By contrast, these mice do not show deficits in the water maze, a spatial task dependent on the hippocampus, where stathmin is not normally expressed. We therefore conclude that stathmin is required for the induction of LTP in afferent inputs to the amygdala and is essential in regulating both innate and learned fear.

Amygdala↗
PubMed2006

Structure and thermodynamics of the tubulin-stathmin interaction.

Oncoprotein 18/stathmin (stathmin) is a phosphorylation-controlled key regulator of microtubule dynamics. In recent years, substantial efforts were undertaken to characterize the complex formed between tubulin and the intrinsically disordered stathmin molecule. Here, I summarize and illustrate the current structural and thermodynamic studies on the tubulin-stathmin interaction. Based on these and on functional information I formulate an updated molecular mechanism on how tubulin-binding by stathmin regulates microtubule dynamics.

Amino Acid Sequence↗
PubMed2004

Differential localization of decidual stathmin during pregnancy in rats.

The present study was undertaken to determine the precise localization of stathmin, a protein associated with microtubule dynamics, during decidualization in rat uterus and to compare it with that of cyclin D3. Immunohistochemical analysis revealed that stathmin is exclusively localized in decidual cells, especially in the primary decidual zone surrounding the embryo, on days 7 and 9 of pregnancy. The intensity of staining was much higher on day 9 than day 7. On day 14, when the endometrial stromal cells had completely differentiated into decidual cells, the staining of decidual cells was faint. Cyclin D3 was expressed in decidual cells of the secondary but not the primary decidual zone on days 7 and 9. On day 14, cyclin D3 levels were low in decidua. Proliferating cell nuclear antigen (PCNA) was broadly detected in the uterus on days 7 and 9, and in the placenta and fetus on day 14. In an artificial decidualization model, cyclin D3 expression was stimulated as deciduoma was formed after an artificial stimulus. Stathmin mRNA levels also increased within 24 h and peaked at 48 h. The specific spatio-temporal uterine expression of stathmin and cyclin D3 suggest that they have a specific role in decidualization in rats.

Animals↗
PubMed2004

Dysregulation of stathmin, a microtubule-destabilizing protein, and up-regulation of Hsp25, Hsp27, and the antioxidant peroxiredoxin 6 in a mouse model of familial amyotrophic lateral sclerosis.

Gain-of-function mutations of the Cu/Zn superoxide dismutase (SOD1) gene cause dominantly inherited familial amyotrophic lateral sclerosis. The identification of differentially regulated proteins in spinal cords of paralyzed mice expressing SOD1(G93A) may contribute to understanding mechanisms of toxicity by mutant SOD1. Protein profiling showed dysregulation of Stathmin with a marked decrease of its most acidic and phosphorylated isoform, and up-regulation of heat shock proteins 25 and 27, peroxiredoxin 6, phosphatidylinositol transfer protein-alpha, apolipoprotein E, and ferritin heavy chain. Stathmin accumulated in the cytoplasm of 30% of spinal cord motor neurons with fragmented Golgi apparatus. Overexpression of Stathmin in HeLa cells was associated with collapse of microtubule networks and Golgi fragmentation. These results, together with the decrease of one Stathmin isoform, suggest a role of the protein in Golgi fragmentation. Mutant SOD1 co-precipitated and co-localized with Hsp25 in neurons and astrocytes. Mutant SOD1 may thus deprive cells of the anti-apoptotic and other protective activities of Hsp25. Astrocytes contained peroxiredoxin 6, a unique nonredundant antioxidant. The up-regulation of peroxiredoxin 6 probably constitutes a defense to oxidative stress induced by SOD1(G93A). Direct effects of SOD1(G93A) or sequential reactions triggered by the mutant may cause the protein changes.

Amyotrophic Lateral Sclerosis↗
PubMed1997

Stathmin: a tubulin-sequestering protein which forms a ternary T2S complex with two tubulin molecules.

Stathmin is an important regulatory protein thought to control the dynamics of microtubules through the cell cycle in a phosphorylation-dependent manner. Here we show that stathmin interacts with two molecules of dimeric alphabeta-tubulin to form a tight ternary T2S complex, sedimenting at 7.7 S. This complex appears in slow association-dissociation equilibrium in the analytical ultracentrifuge. The T2S complex is formed under a variety of ionic conditions, either from GTP- or GDP-tubulin or from the tubulin-colchicine complex. The S16/25/38/63E mutated stathmin in contrast is in rapid equilibrium with tubulin in the T2S complex. The T2S complex cannot polymerize in microtubules nor in ring oligomers. Stathmin acts as a pure tubulin-sequestering protein via formation of the T2S complex. It does not act directly on microtubule ends to promote catastrophe nor enhance microtubule dynamics.

Animals↗
PubMed1999

Stathmin is involved in S100A4-mediated regulation of cell cycle progression.

S100A4 is a cell proliferation- and cancer metastasis-related gene. Previous studies have shown that over-expression of S100A4 drives the cells into the S-phase of the cell cycle, with concomitant enhancement of p53 detection. This has led to the postulate that S100A4 could be controlling cell cycle progression by sequestering p53 and abrogating its G1-S checkpoint control. Cells induced by S100A4 to enter the S-phase do successfully negotiate the G2-M checkpoint control. Here we show that S100A4 is also involved in the regulation of control at this checkpoint. Stathmin is known to be associated, together with p53 in controlling G2-M transition. We present evidence that the expression of S100A4 and stathmin genes is up regulated in exponentially growing HeLa cells. They are down regulated in parallel when cell proliferation is inhibited by hyperthermia and 4-hydroxynonenal (4-HNE). We postulate that S100A4 might directly induce stathmin up regulation to enable cells to enter into mitosis. Since wild-type p53 is known to down regulate stathmin expression, we further postulate this might also involve S100A4-mediated sequestration of p53. The expression of heme oxygenase (HO-1), a stress-response protein, has been used to monitor effects of hyperthermia, 12-O-tetradecanoly phorbol 13-acetate (TPA) and 4-HNE. All these treatments induced HO-1 and also when cells growing in serum-deficiency were restored with full serum. HO-1 induction occurred irrespective of S100A4 expression status. HO-1 gene has responsive elements for many angiogenic agents and induces marked neovascularisation of tumours. We suggest therefore that S100A4 may not possess angiogenic properties.

3T3 Cells↗
PubMed2003

Identification of cJun-responsive genes in Rat-1a cells using multiple techniques: increased expression of stathmin is necessary for cJun-mediated anchorage-independent growth.

cJun is a major component of the transcription factor AP-1 and mediates a diverse set of biologic properties including proliferation, differentiation, and apoptosis. To identify cJun-responsive genes, we inducibly expressed cJun in Rat-1a cells and observed two distinct phenotypes: changes in cellular morphology with adherent growth and anchorage-independent growth. The biologic effects of cJun were entirely reversible demonstrating that they require the continued presence of cJun. To determine the genes, which mediate the biologic effects of cJun, we employed multiple methods including differential gene analysis, suppression subtractive hybridization, and cDNA microarrays. We identified 38 cJun-responsive genes including three uncharacterized genes under adherent and/or nonadherent conditions. Half of the known 36 genes were cytoskeleton- and adhesion-related genes, suggesting a major role of cJun in the regulation of the genes related to cell morphology. As proof of the principle that this approach could identify genes whose upregulation was necessary for nonadherent growth, we investigated one gene, stathmin whose upregulation by cJun was observed only under these conditions. Although overexpression of stathmin did not result in nonadherent growth, inhibition of stathmin protein expression by antisense oligonucleotides in cJun-induced Rat-1a cells prevented nonadherent growth. These results suggest that stathmin plays an essential role in anchorage-independent growth by cJun and may be a potential target for specific inhibitors for AP-1-dependent processes involved in carcinogenesis.

Animals↗
PubMed1994

Molecular characterization of human stathmin expressed in Escherichia coli: site-directed mutagenesis of two phosphorylatable serines (Ser-25 and Ser-63).

Stathmin, a probable relay protein possibly integrating multiple intracellular regulatory signals [reviewed in Sobel (1991) Trends Biochem. Sci. 16, 301-305], was expressed in Escherichia coli at levels as high as 20% of total bacterial protein. Characterization of the purified recombinant protein revealed that it had biochemical properties very similar to those of the native protein. It is a good substrate for both cyclic AMP-dependent protein kinase (PKA) and p34cdc2, on the same four sites as the native eukaryotic protein. As shown by m.s., the difference in isoelectric points from the native protein is probably due to the absence of acetylation of the protein produced in bacteria. C.d. studies indicate that stathmin probably contains about 45% of its sequence in an alpha-helical conformation, as also predicted for the sequence between residues 47 and 124 by computer analysis. Replacement of Ser-63 by alanine by in vitro mutagenesis resulted in a ten times less efficient phosphorylation of stathmin by PKA which occurred solely on Ser-16, confirming that Ser-63 is the major target of this kinase. Replacement of Ser-25, the major site phosphorylated by mitogen-activated protein kinase in vitro and in vivo, by the charged amino acid glutamic acid reproduced, in conjunction with the phosphorylation of Ser-16 by PKA, the mobility shift on SDS/polyacrylamide gels induced by the phosphorylation of Ser-25. This result strongly suggests that glutamic acid in position 25 is able to mimic the putative interactions of phosphoserine-25 with phosphoserine-16, as well as the resulting conformational changes that are probably also related to the functional regulation of stathmin.

Base Sequence↗
PubMed1998

SCLIP: a novel SCG10-like protein of the stathmin family expressed in the nervous system.

Stathmin is a cytosolic phosphoprotein previously described as a ubiquitous relay integrating various signaling pathways. It is the generic element of a protein family in mammals as in Xenopus, including SCG10, a neuron-specific, growth-associated protein, and RB3/XB3, related to the expression of differentiated functions of mature cells of the nervous system. In an extensive search for other members of the stathmin family, we identified cDNAs coding for two novel stathmin-related proteins: (a) a cDNA from a rat striatum cDNA library codes for RB3", a splice variant of RB3, with an additional basic domain in its N-terminal region; and (b) another cDNA identified through a systematic search in EST databases codes for a novel protein, SCLIP, for "SCG10-like protein," displaying 70% identity with SCG10 and sharing the same domain organization, with an N-terminal domain likely involved in membrane attachment and a C-terminal stathmin-like domain. Northern blot analysis as well as in situ hybridization on 14-day rat embryos showed that SCLIP mRNA is expressed only in neural structures. SCLIP mRNA is expressed at comparable levels in neonatal and adult rat brain, suggesting a potential role not only in the acquisition, but also in the expression of differentiated neuronal functions.

Alternative Splicing↗
PubMed1999

Stage-specific expression of a Schistosoma mansoni polypeptide similar to the vertebrate regulatory protein stathmin.

The ubiquitous vertebrate protein stathmin is expressed and phosphorylated in response to a variety of external and internal signals. Stathmin, in turn, controls cell growth and differentiation through its capacity to regulate microtubule assembly dynamics. This is the first report on the molecular cloning and characterization of a stathmin-like protein (SmSLP) in an invertebrate, the human blood fluke Schistosoma mansoni. SmSLP is first synthesized at high levels in the intermediate molluscan host and completely disappears 48 h after penetration into the mammalian host. The protein is preferentially iodinated in intact immature parasites using the Bolton-Hunter reagent, can be quantitatively extracted in high salt buffers, and remains soluble after boiling. Native SmSLP was partially sequenced, and its complete structure was derived from the cloning and sequencing of its cDNA. The sequence is up to 26% identical to vertebrate stathmin sequences and contains two potential phosphorylation sites. Native SmSLP is indeed phosphorylated because phosphatase digestion shifts its mobility in electrofocusing gels. SmSLP associates with tubulin, as suggested by immune co-precipitation results. In vitro experiments demonstrated that SmSLP inhibits tubulin assembly and causes the depolymerization of preassembled microtubules, thus probably fulfilling regulatory roles in critical steps of schistosome development.

Amino Acid Sequence↗
PubMed1997

Upregulation of stathmin (p19) gene expression in adult rat brain during injury-induced synapse formation.

Stathmin (p19) is developmentally regulated as a neural-enriched phosphoprotein associated with neurite outgrowth and synaptic formation during cell proliferation and differentiation, and remains highly abundant in adult rat brain. Whether stathmin is involved in injury-induced reactive synaptogenesis in adult rat was examined in this study. Following unilateral cortical lesion, a significant increase in stathmin mRNA expression was found in the cells of contralateral homotypic cortex and in the subventricular zone of the lateral ventricle. This increase coincided in time with the corticostriatal axon sprouting and synaptic remodeling previously found in denervated striatum. Our data suggest that stathmin plays an important role in regulation of reactive synaptogenesis in adult brain.

Animals↗
PubMed2006

Stathmin-deficient mice develop fibrosis and show delayed recovery from ischemic-reperfusion injury.

In kidneys subjected to ischemic reperfusion injury (IRI) stathmin, a tubulin-binding protein involved in the regulation of mitosis, is expressed in dedifferentiated and proliferating renal tubule cells during the recovery phase. To ascertain the role of stathmin in the recovery from ischemic kidney injury, stathmin-deficient (OP18-/-) and wild-type (WT) animals were subjected to experimental IRI. At 3, 7, and 14 days after reperfusion serum samples and kidneys were collected for the examination of parameters of renal function, morphology, and recovery. Our studies indicate that on day 14 after reperfusion OP18-/- mice have significant renal failure, whereas the creatinine levels of WT animals have returned to baseline. Compared with WT animals OP18-/- mice had more extensive tubular fibrosis. The examination of proliferating cell nuclear antigen expression indicated that OP18-/- animals have increased proliferative or DNA repair activity for a more prolonged duration. The OP18-/- animals also had an increased number of tubules with apoptotic cells. These results suggest that in stathmin-deficient mice subjected to IRI, the aberrant regulation of cell cycle progression, not observed under normal conditions, impairs or at least delays the process of tubular repair and recovery after acute renal injury.

Animals↗
PubMed1990

Phosphorylation of stathmin and other proteins related to nerve growth factor-induced regulation of PC12 cells.

We previously identified a set of soluble proteins whose phosphorylation could be originally related to the multihormonal regulations of anterior pituitary cells. Among these proteins, stathmin (proteins 7 and 8) was found to be ubiquitous and mostly abundant in neurons. Interestingly, stathmin and some other phosphoproteins of the same set could be identified also in PC12 cells in culture. Their phosphorylation was stimulated in these cells by nerve growth factor (NGF) in a way associated with its short term actions, probably corresponding to the early steps of its neuronal differentiating activity. In addition, the same proteins had their phosphorylation stimulated in the presence of fibroblast growth factor, known to stimulate PC12 cell differentiation in a way similar to NGF. A pharmacological analysis allowed us to distinguish three characteristic subsets of phosphoproteins, respectively, affected by cAMP-dependent agents, by cAMP-independent ones, or by both types of agents. Moreover, phosphorylation of stathmin and some other proteins was additive in the presence of NGF and of the cAMP-promoting agent forskolin. Altogether, the present results unravel some intracellular mechanisms related to the regulation of PC12 cells by extracellular effectors. They extend to the regulation of cell differentiation in our recent model for stathmin (Sobel, A., Boutterin, M-C., Beretta, L., Chneiweiss, H., Doye, V., and Peyro-Saint-Paul, H. (1989) J. Biol. Chem. 264, 3765-3772) as an ubiquitous intracellular relay possibly integrating the actions of diverse second messenger pathways involved in cell regulations.

Adenosine↗
PubMed1989

A single cDNA encodes two isoforms of stathmin, a developmentally regulated neuron-enriched phosphoprotein.

Stathmin, a 19-kDa neuron-enriched soluble phosphoprotein, has been recently proposed as an ubiquitous intracellular relay for the diverse extracellular signals regulating cell proliferation, differentiation, and functions through various second messenger pathways (Sobel, A., Boutterin, M.C., Beretta, L., Chneiweiss, H., Doye, V., and peyro-Saint-Paul, H. (1989) J. Biol. Chem. 264, 3765-3772). Internal sequences of the protein from rat brain were determined after purification by two-dimensional polyacrylamide gel electrophoresis, electrotransfer onto Immobilon, and in situ proteolysis. Oligonucleotide mixtures based on these sequences were used to clone a cDNA for stathmin from a rat PC12 cell lambda gt 10 library. The deduced amino acid sequence reveals partial homologies with the coiled coil structural regions of several intracellular matrix phosphoproteins. Using this cDNA as a probe, we show that the expression of stathmin mRNA parallels that of the protein during brain ontogenesis, reaching a maximum at the neonatal stage. In vitro translation of the derived cRNA yielded all the known molecular forms of stathmin, namely its alpha and beta isoforms in their unphosphorylated and phosphorylated states. Thus, a single cDNA codes for both biologically relevant isoforms of the protein, indicating that they differ by co- or post-translational modifications.

Adrenal Gland Neoplasms↗