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Gene Review

STMN1  -  stathmin 1

Homo sapiens

Synonyms: C1orf215, FLJ32206, LAP18, Lag, Leukemia-associated phosphoprotein p18, ...
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Disease relevance of STMN1

  • PUMA overexpression induces reactive oxygen species generation and proteasome-mediated stathmin degradation in colorectal cancer cells [1].
  • 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 [2].
  • Overexpression of stathmin in oral squamous-cell carcinoma: correlation with tumour progression and poor prognosis [3].
  • When messenger ribonuleic acid from human osteosarcoma (Saos-2) cells treated with 10(-8)M 1,25-dihydroxyvitamin D3 was compared with that of cells treated with vehicle alone by this method, we observed an increase in the intensity of a band that on subsequent DNA sequence analysis was found to encode stathmin [4].
  • Decreased protein levels of stathmin in adult brains with Down syndrome and Alzheimer's disease [5].

Psychiatry related information on STMN1

  • Patients versus controls showed significantly: lower Lag Phase and Vitamin E (Vit E) concentrations in plasma and low-density lipoproteins (LDL), higher LDL thiobarbituric acid reactive substances (TBARS), higher fatigue and lower muscle pain thresholds to electrical stimulation [6].
  • Effects of a Lag 1 reinforcement schedule on appropriate and varied responding to the social question, "What do you like to do?" and effects of the proportion of preferred stimuli present during training on the amount of varied responding in each session were investigated with students with autism [7].

High impact information on STMN1


Chemical compound and disease context of STMN1

  • In malignant T lymphoma cells, dephosphorylation and nuclear translocation of pp19/cofilin occur spontaneously through constitutive activation of a serine phosphatase [11].
  • Treatment of the neuroblastoma cell line SMS-KCNR, which contains 75 copies of the N-myc gene, with retinoic acid for ten days resulted in an increase in Op18 phosphorylation [12].
  • In this study we analyzed the level of unphosphorylated Op18 and of its major phosphorylated forms, Op18a and Op18b, in a series of 177 childhood acute leukemias by means of quantitative two-dimensional polyacrylamide gel electrophoresis (2-D PAGE) [13].
  • Persistent growth of BALB/C mouse plasmacytoma and human myeloma cell lines in the presence of phorbol myristate acetate is associated with continued expression of Lap18 (stathmin) [14].

Biological context of STMN1

  • Stathmin is a ubiquitous cytosolic phosphoprotein participating in the relay and integration of diverse intracellular signaling pathways involved in the control of cell proliferation, differentiation, and activities [15].
  • Our results suggest that the interaction of stathmin with Hsc70 is specific in both proteins and most likely biologically relevant in the context of their functional implication in the control of numerous intracellular signaling and regulatory pathways, and hence of normal cell growth and differentiation [15].
  • Cell-cycle-regulated phosphorylation of oncoprotein 18 on Ser16, Ser25 and Ser38 [16].
  • Moreover, during mitosis, a burst of phosphorylation was observed and at this stage of the cell cycle a major fraction of Op18 was phosphorylated at multiple sites [16].
  • Phosphorylation of Op18 during mitosis was located primarily on Ser38 and to lesser extent on Ser25, Ser16 and at an unidentified C-terminal residue [16].

Anatomical context of STMN1

  • Altogether, our results demonstrate in vivo the functional conservation of the stathmin domain within each protein of the stathmin family, with a microtubule destabilizing activity most likely essential for their specific biological function(s) [17].
  • We have identified two serine residues of Op18 that are phosphorylated after triggering by the T cell antigen receptor [16].
  • Treatment of K562 leukemia cell line with hemin that induces terminal differentiation resulted in decreased expression of Op18 [18].
  • The oncoprotein 18 (Op18) gene encodes a proliferation-related cytosolic phosphoprotein, which is induced in normal lymphocytes following mitogenic stimulation [18].
  • Effects of quercetin on heat-induced phosphorylation of stathmin in JURKAT cells were examined [19].

Associations of STMN1 with chemical compounds

  • Transient expression of each of the neural phosphoproteins of the stathmin family showed that they are at least partially associated to the Golgi apparatus and not to other major membrane compartments, probably through their different NH2-terminal domains, as described for SCG10 [17].
  • We have recently identified two distinct proline-directed kinase families that phosphorylates Op18 with overlapping but distinct site preference [20].
  • We also demonstrate that Ser-16 of Op18 is specifically phosphorylated in response to the Ca2+ signal generated by CD3 stimulation or by the Ca2+ ionophore ionomycin [20].
  • Immunoblot analysis of phosphorylated stathmin showed that heat-induced phosphorylation at Ser-38 was inhibited by quercetin but not by staurosporine [19].
  • 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 [2].
  • Loss of stathmin expression increased responsiveness of tumor cells to the treatment with cytostatic drugs targeting MT-stability (paclitaxel, vinblastine) and to DNA cross-linking agents (cisplatin) [21].

Physical interactions of STMN1

  • Hsc70 is among the proteins coimmunoprecipitated with stathmin, and it is the main protein retained specifically on stathmin-Sepharose beads identified by one- and two-dimensional electrophoresis and immunoblots [15].
  • Rac/Cdc42 and p65PAK regulate the microtubule-destabilizing protein stathmin through phosphorylation at serine 16 [22].
  • The aim of this study was to probe the native structure of stathmin and to delineate its minimal region able to interact with tubulin [23].
  • We further demonstrate that DOCK7 and Rac activation lead to phosphorylation and inactivation of the microtubule destabilizing protein stathmin/Op18 in the nascent axon and that this event is important for axon development [24].
  • We further identified two PPIL1-interacting proteins, SNW1/SKIP (SKI-binding protein) and stathmin [25].

Enzymatic interactions of STMN1

  • In transient expression studies, we found that in addition to different stimuli osmotic stress activates p38 delta to phosphorylate stathmin [26].
  • These results strongly suggest that heat stress activates Cdk-1 which phosphorylates Ser 37 on the stathmin molecule [27].

Regulatory relationships of STMN1


Other interactions of STMN1

  • These findings raised the possibility that Op18 may be a substrate for both receptor-regulated calcium-induced protein kinases and the MAP kinase family, as well as being a substrate for the cell-cycle-regulated cdc2 kinase family [16].
  • These findings suggest that Op18 may be a physiological substrate for several members of the cdc2 kinase family during both the S-phase and the mitotic phase of the cell cycle [16].
  • In vivo, the transient expression of neural phosphoproteins of the stathmin family leads to their localization at Golgi membranes and, as previously described for stathmin and SCG10, to the depolymerization of interphasic microtubules [31].
  • The substantial expression of SCLIP in most tissues points out a novel function for this protein outside the nervous system and raises the possibility that its coexpression with stathmin could provide some degree of functional redundancy [32].
  • Serine 25 of oncoprotein 18 is a major cytosolic target for the mitogen-activated protein kinase [33].

Analytical, diagnostic and therapeutic context of STMN1


  1. PUMA overexpression induces reactive oxygen species generation and proteasome-mediated stathmin degradation in colorectal cancer cells. Liu, Z., Lu, H., Shi, H., Du, Y., Yu, J., Gu, S., Chen, X., Liu, K.J., Hu, C.A. Cancer Res. (2005) [Pubmed]
  2. Molecular characterization of human stathmin expressed in Escherichia coli: site-directed mutagenesis of two phosphorylatable serines (Ser-25 and Ser-63). Curmi, P.A., Maucuer, A., Asselin, S., Lecourtois, M., Chaffotte, A., Schmitter, J.M., Sobel, A. Biochem. J. (1994) [Pubmed]
  3. Overexpression of stathmin in oral squamous-cell carcinoma: correlation with tumour progression and poor prognosis. Kouzu, Y., Uzawa, K., Koike, H., Saito, K., Nakashima, D., Higo, M., Endo, Y., Kasamatsu, A., Shiiba, M., Bukawa, H., Yokoe, H., Tanzawa, H. Br. J. Cancer (2006) [Pubmed]
  4. Human and rat osteoblast-like cells express stathmin, a growth-regulatory protein. Kumar, R., Haugen, J.D. Biochem. Biophys. Res. Commun. (1994) [Pubmed]
  5. Decreased protein levels of stathmin in adult brains with Down syndrome and Alzheimer's disease. Cheon, M.S., Fountoulakis, M., Cairns, N.J., Dierssen, M., Herkner, K., Lubec, G. J. Neural Transm. Suppl. (2001) [Pubmed]
  6. Relationship between musculoskeletal symptoms and blood markers of oxidative stress in patients with chronic fatigue syndrome. Vecchiet, J., Cipollone, F., Falasca, K., Mezzetti, A., Pizzigallo, E., Bucciarelli, T., De Laurentis, S., Affaitati, G., De Cesare, D., Giamberardino, M.A. Neurosci. Lett. (2003) [Pubmed]
  7. The effects of lag schedules and preferred materials on variable responding in students with autism. Lee, R., Sturmey, P. Journal of autism and developmental disorders. (2006) [Pubmed]
  8. The oncoprotein 18/stathmin family of microtubule destabilizers. Cassimeris, L. Curr. Opin. Cell Biol. (2002) [Pubmed]
  9. Transcriptional repression by wild-type p53 utilizes histone deacetylases, mediated by interaction with mSin3a. Murphy, M., Ahn, J., Walker, K.K., Hoffman, W.H., Evans, R.M., Levine, A.J., George, D.L. Genes Dev. (1999) [Pubmed]
  10. p27(Kip1) and stathmin share the stage for the first time. Iancu-Rubin, C., Atweh, G.F. Trends Cell Biol. (2005) [Pubmed]
  11. Inhibition of constitutive serine phosphatase activity in T lymphoma cells results in phosphorylation of pp19/cofilin and induces apoptosis. Samstag, Y., Dreizler, E.M., Ambach, A., Sczakiel, G., Meuer, S.C. J. Immunol. (1996) [Pubmed]
  12. N-myc gene amplification in neuroblastoma is associated with altered phosphorylation of a proliferation related polypeptide (Op18). Hailat, N., Strahler, J., Melhem, R., Zhu, X.X., Brodeur, G., Seeger, R.C., Reynolds, C.P., Hanash, S. Oncogene (1990) [Pubmed]
  13. Quantitative analysis of Op18 phosphorylation in childhood acute leukemia. Melhem, R., Hailat, N., Kuick, R., Hanash, S.M. Leukemia (1997) [Pubmed]
  14. Persistent growth of BALB/C mouse plasmacytoma and human myeloma cell lines in the presence of phorbol myristate acetate is associated with continued expression of Lap18 (stathmin). Jones, N.A., Rowlands, D.C., Johnson, W.E., MacLennan, I.C., Brown, G. Hematological oncology. (1995) [Pubmed]
  15. Stathmin interaction with HSC70 family proteins. Manceau, V., Gavet, O., Curmi, P., Sobel, A. Electrophoresis (1999) [Pubmed]
  16. Cell-cycle-regulated phosphorylation of oncoprotein 18 on Ser16, Ser25 and Ser38. Brattsand, G., Marklund, U., Nylander, K., Roos, G., Gullberg, M. Eur. J. Biochem. (1994) [Pubmed]
  17. The stathmin phosphoprotein family: intracellular localization and effects on the microtubule network. Gavet, O., Ozon, S., Manceau, V., Lawler, S., Curmi, P., Sobel, A. J. Cell. Sci. (1998) [Pubmed]
  18. Characterization of the gene for a proliferation-related phosphoprotein (oncoprotein 18) expressed in high amounts in acute leukemia. Melhem, R.F., Zhu, X.X., Hailat, N., Strahler, J.R., Hanash, S.M. J. Biol. Chem. (1991) [Pubmed]
  19. Inhibition of heat-induced phosphorylation of stathmin by the bioflavonoid quercetin. Nagasaka, Y., Fijimoto, M., Arai, H., Nakamura, K. Electrophoresis (2002) [Pubmed]
  20. Multiple signal transduction pathways induce phosphorylation of serines 16, 25, and 38 of oncoprotein 18 in T lymphocytes. Marklund, U., Brattsand, G., Osterman, O., Ohlsson, P.I., Gullberg, M. J. Biol. Chem. (1993) [Pubmed]
  21. Protumorigenic overexpression of stathmin/Op18 by gain-of-function mutation in p53 in human hepatocarcinogenesis. Singer, S., Ehemann, V., Brauckhoff, A., Keith, M., Vreden, S., Schirmacher, P., Breuhahn, K. Hepatology (2007) [Pubmed]
  22. Rac/Cdc42 and p65PAK regulate the microtubule-destabilizing protein stathmin through phosphorylation at serine 16. Daub, H., Gevaert, K., Vandekerckhove, J., Sobel, A., Hall, A. J. Biol. Chem. (2001) [Pubmed]
  23. Probing the native structure of stathmin and its interaction domains with tubulin. Combined use of limited proteolysis, size exclusion chromatography, and mass spectrometry. Redeker, V., Lachkar, S., Siavoshian, S., Charbaut, E., Rossier, J., Sobel, A., Curmi, P.A. J. Biol. Chem. (2000) [Pubmed]
  24. The Rac Activator DOCK7 Regulates Neuronal Polarity through Local Phosphorylation of Stathmin/Op18. Watabe-Uchida, M., John, K.A., Janas, J.A., Newey, S.E., Van Aelst, L. Neuron (2006) [Pubmed]
  25. Overexpression of peptidyl-prolyl isomerase-like 1 is associated with the growth of colon cancer cells. Obama, K., Kato, T., Hasegawa, S., Satoh, S., Nakamura, Y., Furukawa, Y. Clin. Cancer Res. (2006) [Pubmed]
  26. Identification of stathmin as a novel substrate for p38 delta. Parker, C.G., Hunt, J., Diener, K., McGinley, M., Soriano, B., Keesler, G.A., Bray, J., Yao, Z., Wang, X.S., Kohno, T., Lichenstein, H.S. Biochem. Biophys. Res. Commun. (1998) [Pubmed]
  27. Analysis on heat stress-induced hyperphosphorylation of stathmin at serine 37 in Jurkat cells by means of two-dimensional gel electrophoresis and tandem mass spectrometry. Nakamura, K., Zhang, X., Kuramitsu, Y., Fujimoto, M., Yuan, X., Akada, J., Aoshima-Okuda, M., Mitani, N., Itoh, Y., Katoh, T., Morita, Y., Nagasaka, Y., Yamazaki, Y., Kuriki, T., Sobel, A. Journal of chromatography. A. (2006) [Pubmed]
  28. Analysis of heat shock-induced monophosphorylation of stathmin in human T lymphoblastic cell line JURKAT by two-dimensional gel electrophoresis. Fujimoto, M., Nagasaka, Y., Tanaka, T., Nakamura, K. Electrophoresis (1998) [Pubmed]
  29. Stathmin phosphorylation is regulated in striatal neurons by vasoactive intestinal peptide and monoamines via multiple intracellular pathways. Chneiweiss, H., Cordier, J., Sobel, A. J. Neurochem. (1992) [Pubmed]
  30. Stathmin phosphorylation patterns discriminate between distinct transduction pathways of human T lymphocyte activation through CD2 triggering. le Gouvello, S., Chneiweiss, H., Tarantino, N., Debre, P., Sobel, A. FEBS Lett. (1991) [Pubmed]
  31. Stathmin and its phosphoprotein family: general properties, biochemical and functional interaction with tubulin. Curmi, P.A., Gavet, O., Charbaut, E., Ozon, S., Lachkar-Colmerauer, S., Manceau, V., Siavoshian, S., Maucuer, A., Sobel, A. Cell Struct. Funct. (1999) [Pubmed]
  32. Expression of stathmin family genes in human tissues: non-neural-restricted expression for SCLIP. Bièche, I., Maucuer, A., Laurendeau, I., Lachkar, S., Spano, A.J., Frankfurter, A., Lévy, P., Manceau, V., Sobel, A., Vidaud, M., Curmi, P.A. Genomics (2003) [Pubmed]
  33. Serine 25 of oncoprotein 18 is a major cytosolic target for the mitogen-activated protein kinase. Marklund, U., Brattsand, G., Shingler, V., Gullberg, M. J. Biol. Chem. (1993) [Pubmed]
  34. Control of microtubule dynamics by oncoprotein 18: dissection of the regulatory role of multisite phosphorylation during mitosis. Larsson, N., Marklund, U., Gradin, H.M., Brattsand, G., Gullberg, M. Mol. Cell. Biol. (1997) [Pubmed]
  35. Analysis of phosphoprotein p19 by liquid chromatography/mass spectrometry. Identification of two proline-directed serine phosphorylation sites and a blocked amino terminus. Labdon, J.E., Nieves, E., Schubart, U.K. J. Biol. Chem. (1992) [Pubmed]
  36. Thermodynamics of the Op18/stathmin-tubulin interaction. Honnappa, S., Cutting, B., Jahnke, W., Seelig, J., Steinmetz, M.O. J. Biol. Chem. (2003) [Pubmed]
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