Stathmin

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.

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]

Stathmin
Structure of Tubulin-Colchicine-Vinblastine: Stathmin-like domain complex
Identifiers
Symbol	Stathmin
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 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.[9]

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]

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]

• NLM
• Stathmin.com