Stathmin

Stathmin 1
Identifiers
Symbols	STMN1 ; C1orf215; LAP18; Lag; OP18; PP17; PP19; PR22; SMN
External IDs	OMIM: 151442 MGI: 96739 HomoloGene: 4063 GeneCards: STMN1 Gene
Gene ontology Molecular function • signal transducer activity • protein binding • tubulin binding Cellular component • intracellular • cytoplasm • cytosol • microtubule • membrane • neuron projection • extracellular exosome Biological process • microtubule depolymerization • mitotic spindle organization • signal transduction • axonogenesis • brain development • response to virus • negative regulation of microtubule polymerization • neuron projection development • intracellular signal transduction • positive regulation of cellular component movement • regulation of cytoskeleton organization Sources: Amigo / QuickGO
RNA expression pattern
More reference expression data
Orthologs
Species	Human	Mouse
Entrez	3925	16765
Ensembl	ENSG00000117632	ENSMUSG00000028832
UniProt	P16949	P54227
RefSeq (mRNA)	NM_001145454	NM_019641
RefSeq (protein)	NP_001138926	NP_062615
Location (UCSC)	Chr 1: 25.88 – 25.91 Mb	Chr 4: 134.47 – 134.47 Mb
PubMed search

Stathmin 1/oncoprotein 18, also known as STMN1, is a highly conserved 17 kDa protein. Its function as an important regulatory protein of microtubule dynamics has been well-characterized.^[1] Eukaryotic microtubules are one of three major components of the cell’s cytoskeleton. They are highly dynamic structures that continuously alternate between assembly and disassembly. Stathmin performs an important function in regulating rapid microtubule remodeling of the cytoskeleton in response to the cell’s needs. Microtubules are cylindrical polymers of α,β-tubulin. Their assembly is in part determined by the concentration of free tubulin in the cytoplasm.^[2]

At low concentrations of free tubulin, the growth rate at the microtubule ends is slowed and results in an increased rate of depolymerization (disassembly).^[1][3]

Function

Stathmin interacts with two molecules of dimeric α,β-tubulin to form a tight ternary complex called the T2S complex.^[1] One mole of stathmin binds to two moles of tubulin dimers through the stathmin-like domain (SLD).^[3] When stathmin sequesters tubulin into the T2S complex, tubulin becomes non-polymerizable. Without tubulin polymerization, there is no microtubule assembly.^[1] Stathmin also promotes microtubule disassembly by acting directly on the microtubule ends.^[4]

The rate of microtubule assembly is an important aspect of cell growth therefore associating regulation of stathmin with cell cycle progress. Regulation of stathmin is cell cycle dependent and controlled by the cell’s protein kinases in response to specific cell signals.^[3] Phosphorylation at four serine residues on stathmin named Ser16, Ser25, Ser38 and Ser63 causes weakened stathmin-tubulin binding. Stathmin phosphorylation increases the concentration of tubulin available in the cytoplasm for microtubule assembly. For cells to assemble the mitotic spindle necessary for initiation of the mitotic phase of the cell cycle, stathmin phosphorylation must occur. Without microtuble growth and assembly, the mitotic spindle cannot form, and the cell cycle is arrested. At cytokinesis, the last phase of the cell cycle, rapid dephosphorylation of stathmin occurs to block the cell from entering back into the cell cycle until it is ready.^[3]

Oncoprotein characterization

Stathmin’s role in regulation of the cell cycle causes it to be an oncoprotein named oncoprotein 18 (op18). Stathmin (aka op18) can cause uncontrolled cell proliferation when mutated and not functioning properly. If stathmin is unable to bind to tubulin, it allows for constant microtubule assembly and therefore constant mitotic spindle assembly. With no regulation of the mitotic spindle, the cell cycle is capable of cycling uncontrollably resulting in the unregulated cell growth characteristic of cancer cells.^[3]

Role in social behaviour

Mice without stathmin have deficiency in innate and learned fear. Stathmin−/− females do not assess threats well, leading to lack of innate parental care and adult social interactions. They lack motivation for retrieving pups and are unable to choose a safe location for nest-building. However, they have an enhancement in social interactions.^[5]

References

1. Jourdain L, Curmi P, Sobel A, Pantaloni D, Carlier MF (September 1997). "Stathmin: a tubulin-sequestering protein which forms a ternary T2S complex with two tubulin molecules". Biochemistry 36 (36): 10817–21. doi:10.1021/bi971491b. PMID 9312271.
2. Clément MJ, Jourdain I, Lachkar S, Savarin P, Gigant B, Knossow M, Toma F, Sobel A, Curmi PA (November 2005). "N-terminal stathmin-like peptides bind tubulin and impede microtubule assembly". Biochemistry 44 (44): 14616–25. doi:10.1021/bi0512492. PMID 16262261.
3. Cassimeris L (February 2002). "The oncoprotein 18/stathmin family of microtubule destabilizers". Curr. Opin. Cell Biol. 14 (1): 18–24. doi:10.1016/S0955-0674(01)00289-7. PMID 11792540.
4. Atweh, George F.; Rubin, Camelia Iancu (August 2004). "The Role of Stathmin in the Regulation of the Cell Cycle". Journal of Cellular Biochemistry 93 (2): 242–250. doi:10.1002/jcb.20187. PMID 15368352.
5. Martel G, Nishi A, Shumyatsky GP (September 2008). "Stathmin reveals dissociable roles of the basolateral amygdala in parental and social behaviors". Proc. Natl. Acad. Sci. U.S.A. 105 (38): 14620–5. doi:10.1073/pnas.0807507105. PMC 2567152. PMID 18794533.

Further reading

• Sobel A (1991). "Stathmin: a relay phosphoprotein for multiple signal transduction?". Trends Biochem. Sci. 16 (8): 301–5. doi:10.1016/0968-0004(91)90123-D. PMID 1957351.
• Steinmetz MO (2007). "Structure and thermodynamics of the tubulin-stathmin interaction". J. Struct. Biol. 158 (2): 137–47. doi:10.1016/j.jsb.2006.07.018. PMID 17029844.
• Doye V, Le Gouvello S, Dobransky T, et al. (1992). "Expression of transfected stathmin cDNA reveals novel phosphorylated forms associated with developmental and functional cell regulation". Biochem. J. 287 (Pt 2): 549–54. PMC 1133199. PMID 1445213.
• Labdon JE, Nieves E, Schubart UK (1992). "Analysis of phosphoprotein p19 by liquid chromatography/mass spectrometry. Identification of two proline-directed serine phosphorylation sites and a blocked amino terminus". J. Biol. Chem. 267 (5): 3506–13. PMID 1737801.
• Melhem RF, Zhu XX, Hailat N, et al. (1991). "Characterization of the gene for a proliferation-related phosphoprotein (oncoprotein 18) expressed in high amounts in acute leukemia". J. Biol. Chem. 266 (27): 17747–53. PMID 1917919.
• Ferrari AC, Seuanez HN, Hanash SM, Atweh GF (1991). "A gene that encodes for a leukemia-associated phosphoprotein (p18) maps to chromosome bands 1p35-36.1". Genes Chromosomes Cancer 2 (2): 125–9. doi:10.1002/gcc.2870020208. PMID 2278968.
• Maucuer A, Doye V, Sobel A (1990). "A single amino acid difference distinguishes the human and the rat sequences of stathmin, a ubiquitous intracellular phosphoprotein associated with cell regulations". FEBS Lett. 264 (2): 275–8. doi:10.1016/0014-5793(90)80266-L. PMID 2358074.
• Zhu XX, Kozarsky K, Strahler JR, et al. (1989). "Molecular cloning of a novel human leukemia-associated gene. Evidence of conservation in animal species". J. Biol. Chem. 264 (24): 14556–60. PMID 2760073.
• Sobel A, Boutterin MC, Beretta L, et al. (1989). "Intracellular substrates for extracellular signaling. Characterization of a ubiquitous, neuron-enriched phosphoprotein (stathmin)". J. Biol. Chem. 264 (7): 3765–72. PMID 2917975.
• Maucuer A, Camonis JH, Sobel A (1995). "Stathmin interaction with a putative kinase and coiled-coil-forming protein domains". Proc. Natl. Acad. Sci. U.S.A. 92 (8): 3100–4. doi:10.1073/pnas.92.8.3100. PMC 42112. PMID 7724523.
• Kato S, Sekine S, Oh SW, et al. (1995). "Construction of a human full-length cDNA bank". Gene 150 (2): 243–50. doi:10.1016/0378-1119(94)90433-2. PMID 7821789.
• Curmi PA, Maucuer A, Asselin S, et al. (1994). "Molecular characterization of human stathmin expressed in Escherichia coli: site-directed mutagenesis of two phosphorylatable serines (Ser-25 and Ser-63)". Biochem. J. 300 (Pt 2): 331–8. PMC 1138166. PMID 8002936.
• Kumar R, Haugen JD (1994). "Human and rat osteoblast-like cells express stathmin, a growth-regulatory protein". Biochem. Biophys. Res. Commun. 201 (2): 861–5. doi:10.1006/bbrc.1994.1780. PMID 8003023.
• Brattsand G, Marklund U, Nylander K, et al. (1994). "Cell-cycle-regulated phosphorylation of oncoprotein 18 on Ser16, Ser25 and Ser38". Eur. J. Biochem. 220 (2): 359–68. doi:10.1111/j.1432-1033.1994.tb18632.x. PMID 8125092.
• Marklund U, Brattsand G, Osterman O, et al. (1994). "Multiple signal transduction pathways induce phosphorylation of serines 16, 25, and 38 of oncoprotein 18 in T lymphocytes". J. Biol. Chem. 268 (34): 25671–80. PMID 8245003.
• Marklund U, Brattsand G, Shingler V, Gullberg M (1993). "Serine 25 of oncoprotein 18 is a major cytosolic target for the mitogen-activated protein kinase". J. Biol. Chem. 268 (20): 15039–47. PMID 8325880.
• Beretta L, Dobránsky T, Sobel A (1993). "Multiple phosphorylation of stathmin. Identification of four sites phosphorylated in intact cells and in vitro by cyclic AMP-dependent protein kinase and p34cdc2". J. Biol. Chem. 268 (27): 20076–84. PMID 8376365.
• Hosoya H, Ishikawa K, Dohi N, Marunouchi T (1997). "Transcriptional and post-transcriptional regulation of pr22 (Op18) with proliferation control". Cell Struct. Funct. 21 (4): 237–43. doi:10.1247/csf.21.237. PMID 8906359.
• Larsson N, Marklund U, Gradin HM, et al. (1997). "Control of microtubule dynamics by oncoprotein 18: dissection of the regulatory role of multisite phosphorylation during mitosis". Mol. Cell. Biol. 17 (9): 5530–9. PMC 232401. PMID 9271428.

External links

• NLM
• Stathmin.com