Stathmin

Last updated
STMN1
Identifiers
Aliases STMN1 , C1orf215, LAP18, Lag, OP18, PP17, PP19, PR22, SMN, stathmin 1
External IDs OMIM: 151442 MGI: 96739 HomoloGene: 4063 GeneCards: STMN1
Orthologs
SpeciesHumanMouse
Entrez
Ensembl
UniProt
RefSeq (mRNA)

NM_203401
NM_001145454
NM_005563
NM_152497
NM_203399

Contents

NM_019641

RefSeq (protein)

NP_001138926
NP_005554
NP_981944
NP_981946

NP_062615

Location (UCSC) Chr 1: 25.88 – 25.91 Mb Chr 4: 134.2 – 134.2 Mb
PubMed search [3] [4]
Wikidata
View/Edit Human View/Edit Mouse

Stathmin, also known as metablastin and oncoprotein 18 is a protein that in humans is encoded by the STMN1 gene.

Stathmin is a highly conserved 17 kDa protein that is crucial for the regulation of the cell cytoskeleton. Changes in the cytoskeleton are important because the cytoskeleton is a scaffold required for many cellular processes, such as cytoplasmic organization, cell division and cell motility. [5] More specifically, stathmin is crucial in regulating the cell cycle. [6] It is found solely in eukaryotes.

Its function as an important regulatory protein of microtubule dynamics has been well-characterized. [7] 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. [8]

At low concentrations of free tubulin, the growth rate at the microtubule ends is slowed and results in an increased rate of depolymerization (disassembly). [7] [9]

Structure

Stathmin, and the related proteins SCG10 and XB3, contain a N-terminal domain (XB3 contains an additional N-terminal hydrophobic region), a 78 amino acid coiled-coil region, and a short C-terminal domain.

Function

The function of Stathmin is to regulate the cytoskeleton of the cell. The cytoskeleton is made up of long hollow cylinders named microtubules. These microtubules are made up of alpha and beta tubulin heterodimers. The changes in cytoskeleton are known as microtubule dynamics; the addition of the tubulin subunits lead to polymerisation and their loss, depolymerisation. [5] Stathmin regulates these by promoting depolymerization of microtubules or preventing polymerization of tubulin heterodimers. [6]

Additionally, Stathmin is thought to have a role in cell signaling pathway. Stathmin is a ubiquitous phosphorylated protein which makes it act as an intracellular relay for diverse regulatory pathways, [10] functioning through a variety of second messengers.

Its phosphorylation and gene expression are regulated throughout development [11] and in response to extracellular signals regulating cell proliferation, differentiation and function. [12]

Interactions

Stathmin
PDB 1z2b EBI.jpg
Structure of Tubulin-Colchicine-Vinblastine: Stathmin-like domain complex
Identifiers
SymbolStathmin
Pfam PF00836
InterPro IPR000956
PROSITE PDOC00487
SCOP2 1sa0 / SCOPe / SUPFAM
Available protein structures:
Pfam   structures / ECOD  
PDB RCSB PDB; PDBe; PDBj
PDBsum structure summary

Stathmin interacts with two molecules of dimeric α,β-tubulin to form a tight ternary complex called the T2S complex. [7] One mole of stathmin binds to two moles of tubulin dimers through the stathmin-like domain (SLD). [9] When stathmin sequesters tubulin into the T2S complex, tubulin becomes non-polymerizable. Without tubulin polymerization, there is no microtubule assembly. [7] Stathmin also promotes microtubule disassembly by acting directly on the microtubule ends. [6]

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. [9] 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 microtubule 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. [9]

Clinical significance

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. [9]

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. [13]

Related Research Articles

<span class="mw-page-title-main">Microtubule</span> Polymer of tubulin that forms part of the cytoskeleton

Microtubules are polymers of tubulin that form part of the cytoskeleton and provide structure and shape to eukaryotic cells. Microtubules can be as long as 50 micrometres, as wide as 23 to 27 nm and have an inner diameter between 11 and 15 nm. They are formed by the polymerization of a dimer of two globular proteins, alpha and beta tubulin into protofilaments that can then associate laterally to form a hollow tube, the microtubule. The most common form of a microtubule consists of 13 protofilaments in the tubular arrangement.

In biochemistry, dephosphorylation is the removal of a phosphate (PO43−) group from an organic compound by hydrolysis. It is a reversible post-translational modification. Dephosphorylation and its counterpart, phosphorylation, activate and deactivate enzymes by detaching or attaching phosphoric esters and anhydrides. A notable occurrence of dephosphorylation is the conversion of ATP to ADP and inorganic phosphate.

<span class="mw-page-title-main">Tau protein</span> Group of six protein isoforms produced from the MAPT gene

The tau proteins are a group of six highly soluble protein isoforms produced by alternative splicing from the gene MAPT. They have roles primarily in maintaining the stability of microtubules in axons and are abundant in the neurons of the central nervous system (CNS), where the cerebral cortex has the highest abundance. They are less common elsewhere but are also expressed at very low levels in CNS astrocytes and oligodendrocytes.

The Casein kinase 1 family of protein kinases are serine/threonine-selective enzymes that function as regulators of signal transduction pathways in most eukaryotic cell types. CK1 isoforms are involved in Wnt signaling, circadian rhythms, nucleo-cytoplasmic shuttling of transcription factors, DNA repair, and DNA transcription.

<span class="mw-page-title-main">PLK1</span> Mammalian protein found in Homo sapiens

Serine/threonine-protein kinase PLK1, also known as polo-like kinase 1 (PLK-1) or serine/threonine-protein kinase 13 (STPK13), is an enzyme that in humans is encoded by the PLK1 gene.

<span class="mw-page-title-main">Calcium/calmodulin-dependent protein kinase type II subunit alpha</span> Protein-coding gene in the species Homo sapiens

Calcium/calmodulin-dependent protein kinase type II subunit alpha (CAMKIIα), a.k.a.Ca2+/calmodulin-dependent protein kinase II alpha, is one subunit of CamKII, a protein kinase (i.e., an enzyme which phosphorylates proteins) that in humans is encoded by the CAMK2A gene.

<span class="mw-page-title-main">PPP2CA</span> Enzyme

Serine/threonine-protein phosphatase 2A catalytic subunit alpha isoform is an enzyme that is encoded by the PPP2CA gene.

<span class="mw-page-title-main">MAP4</span> Protein-coding gene in the species Homo sapiens

Microtubule-associated protein 4 is a protein that in humans is encoded by the MAP4 gene.

<span class="mw-page-title-main">TUBA4A</span> Protein-coding gene in the species Homo sapiens

Tubulin alpha-4A chain is a protein that in humans is encoded by the TUBA4A gene.

<span class="mw-page-title-main">Vasodilator-stimulated phosphoprotein</span> Mammalian protein found in Homo sapiens

Vasodilator-stimulated phosphoprotein is a protein that in humans is encoded by the VASP gene.

<span class="mw-page-title-main">HMGN1</span> Protein-coding gene in the species Homo sapiens

Non-histone chromosomal protein HMG-14 is a protein that in humans is encoded by the HMGN1 gene.

<span class="mw-page-title-main">PPP1R2</span> Protein-coding gene in the species Homo sapiens

Protein phosphatase inhibitor 2 is an enzyme that in humans is encoded by the PPP1R2 gene.

<span class="mw-page-title-main">STMN2</span> Protein-coding gene in the species Homo sapiens

Stathmin-2 is a protein that in humans is encoded by the STMN2 gene.

<span class="mw-page-title-main">Protein phosphorylation</span> Process of introducing a phosphate group on to a protein

Protein phosphorylation is a reversible post-translational modification of proteins in which an amino acid residue is phosphorylated by a protein kinase by the addition of a covalently bound phosphate group. Phosphorylation alters the structural conformation of a protein, causing it to become either activated or deactivated, or otherwise modifying its function. Approximately 13000 human proteins have sites that are phosphorylated.

<span class="mw-page-title-main">Ensconsin</span> Protein-coding gene in the species Homo sapiens

Ensconsin is a protein that in humans is encoded by the MAP7 gene.

<span class="mw-page-title-main">STMN3</span> Protein-coding gene in the species Homo sapiens

Stathmin-3 is a protein that in humans is encoded by the STMN3 gene.

<span class="mw-page-title-main">PRKG1</span> Protein-coding gene in the species Homo sapiens

cGMP-dependent protein kinase 1, alpha isozyme is an enzyme that in humans is encoded by the PRKG1 gene.

Catastrophin is a term use to describe proteins that are associated with the disassembly of microtubules. Catastrophins affect microtubule shortening, a process known as microtubule catastrophe.

<span class="mw-page-title-main">Centrosome cycle</span> Centrioles are nine triplets microtubules

Centrosomes are the major microtubule organizing centers (MTOC) in mammalian cells. Failure of centrosome regulation can cause mistakes in chromosome segregation and is associated with aneuploidy. A centrosome is composed of two orthogonal cylindrical protein assemblies, called centrioles, which are surrounded by a protein dense amorphous cloud of pericentriolar material (PCM). The PCM is essential for nucleation and organization of microtubules. The centrosome cycle is important to ensure that daughter cells receive a centrosome after cell division. As the cell cycle progresses, the centrosome undergoes a series of morphological and functional changes. Initiation of the centrosome cycle occurs early in the cell cycle in order to have two centrosomes by the time mitosis occurs.

Edwin W. Taylor is an adjunct professor of cell and developmental biology at Northwestern University. He was elected to the National Academy of Sciences in 2001. Taylor received a BA in physics and chemistry from the University of Toronto in 1952; an MSc in physical chemistry from McMaster University in 1955, and a PhD in biophysics from the University of Chicago in 1957. In 2001 Taylor was elected to the National Academy of Scineces in Cellular and Developmental Biology and Biochemistry.

References

  1. 1 2 3 GRCh38: Ensembl release 89: ENSG00000117632 - Ensembl, May 2017
  2. 1 2 3 GRCm38: Ensembl release 89: ENSMUSG00000028832 - Ensembl, May 2017
  3. "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  4. "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  5. 1 2 Kueh HY, Mitchison TJ (August 2009). "Structural plasticity in actin and tubulin polymer dynamics". Science. 325 (5943): 960–3. Bibcode:2009Sci...325..960K. doi:10.1126/science.1168823. PMC   2864651 . PMID   19696342.
  6. 1 2 3 Rubin CI, Atweh GF (October 2004). "The role of stathmin in the regulation of the cell cycle". Journal of Cellular Biochemistry. 93 (2): 242–50. doi:10.1002/jcb.20187. PMID   15368352. S2CID   406185.
  7. 1 2 3 4 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.
  8. 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.
  9. 1 2 3 4 5 Cassimeris L (February 2002). "The oncoprotein 18/stathmin family of microtubule destabilizers". Current Opinion in Cell Biology. 14 (1): 18–24. doi:10.1016/S0955-0674(01)00289-7. PMID   11792540.
  10. Maucuer A, Doye V, Sobel A (May 1990). "A single amino acid difference distinguishes the human and the rat sequences of stathmin, a ubiquitous intracellular phosphoprotein associated with cell regulations". FEBS Letters. 264 (2): 275–8. doi: 10.1016/0014-5793(90)80266-L . PMID   2358074. S2CID   30922217.
  11. Maucuer A, Moreau J, Méchali M, Sobel A (August 1993). "Stathmin gene family: phylogenetic conservation and developmental regulation in Xenopus". The Journal of Biological Chemistry. 268 (22): 16420–9. doi: 10.1016/S0021-9258(19)85437-6 . PMID   8344928.
  12. Doye V, Soubrier F, Bauw G, Boutterin MC, Beretta L, Koppel J, Vandekerckhove J, Sobel A (July 1989). "A single cDNA encodes two isoforms of stathmin, a developmentally regulated neuron-enriched phosphoprotein". The Journal of Biological Chemistry. 264 (21): 12134–7. doi: 10.1016/S0021-9258(18)63830-X . PMID   2745432.
  13. Martel G, Nishi A, Shumyatsky GP (September 2008). "Stathmin reveals dissociable roles of the basolateral amygdala in parental and social behaviors". Proceedings of the National Academy of Sciences of the United States of America. 105 (38): 14620–5. Bibcode:2008PNAS..10514620M. doi: 10.1073/pnas.0807507105 . PMC   2567152 . PMID   18794533.

Further reading

This article incorporates text from the public domain Pfam and InterPro: IPR000956