Stathmin

Stathmin 1/oncoprotein 18, also known as STMN1, is a highly conserved 17 kDa is_associated_with::protein. Its function as an important regulatory protein of is_associated_with::microtubule dynamics has been well-characterized. Eukaryotic microtubules are one of three major components of the cell’s is_associated_with::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 is_associated_with::tubulin in the is_associated_with::cytoplasm.

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

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

The rate of microtubule assembly is an important aspect of cell growth therefore associating regulation of stathmin with is_associated_with::cell cycle progress. Regulation of stathmin is cell cycle dependent and controlled by the cell’s is_associated_with::protein kinases in response to specific cell signals. is_associated_with::Phosphorylation at four serine residues on stathmin named is_associated_with::Ser16, is_associated_with::Ser25, is_associated_with::Ser38 and is_associated_with::Ser63 causes weakened stathmin-tubulin binding. Stathmin is_associated_with::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 is_associated_with::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.

Oncoprotein characterization
Stathmin’s role in regulation of the cell cycle causes it to be an oncoprotein named is_associated_with::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 is_associated_with::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 is_associated_with::cancer cells.

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.