Beta III Tubulin Rabbit Polyclonal Antibody

Function

Tubulin is the major constituent of microtubules. It binds two moles of GTP, one at an exchangeable site on the beta chain and one at a non-exchangeable site on the alpha chain. TUBB3 plays a critical role in proper axon guidance and mantainance. It has been reported that β3-tubulin is expressed in a wide variety of tumors. Overexpression of this isotype in clinical samples correlates with tumor aggressiveness, resistance to chemotherapeutic drugs, and poor patient survival. The β3 isotype increases tumor aggressiveness by two distinct mechanisms. Incorporation of this isotype makes microtubule networks hypostable, allowing them to resist the cytotoxic effects of microtubule stabilizing drugs like taxanes or epothilones. Mechanistically, it was found that overexpression of β3-tubulin increases the rate of microtubule detachment from microtubule organizing centers, an activity that is suppressed by drugs such as paclitaxel.

Background References

1. "Class III beta-tubulin isotype: a key cytoskeletal protein at the crossroads of developmental neurobiology and tumor neuropathology." Katsetos C.D., Legido A., Perentes E., Mork S.J. J. Child Neurol. 18:851-866(2003)

2. "Tumoral and tissue-specific expression of the major human beta-tubulin isotypes." Leandro-Garcia L.J., Leskela S., Landa I., Montero-Conde C., Lopez-Jimenez E., Leton R., Cascon A., Robledo M., Rodriguez-Antona C. Cytoskeleton 67:214-223(2010)

3. "Mutations in the neuronal ss-tubulin subunit TUBB3 result in malformation of cortical development and neuronal migration defects." Poirier K., Saillour Y., Bahi-Buisson N., Jaglin X.H., Fallet-Bianco C., Nabbout R., Castelnau-Ptakhine L., Hum. Mol. Genet. 19:4462-4473(2010)

Sequence Similarity

Belongs to the tubulin family.

Tissue Specificity

Expression is primarily restricted to central and peripheral nervous system. Greatly increased expression in most cancerous tissues.

Post-translational Modification

Some glutamate residues at the C-terminus are polyglutamylated, resulting in polyglutamate chains on the gamma-carboxyl group. Polyglutamylation plays a key role in microtubule severing by spastin (SPAST). SPAST preferentially recognizes and acts on microtubules decorated with short polyglutamate tails: severing activity by SPAST increases as the number of glutamates per tubulin rises from one to eight, but decreases beyond this glutamylation threshold.; Some glutamate residues at the C-terminus are monoglycylated but not polyglycylated due to the absence of functional TTLL10 in human. Monoglycylation is mainly limited to tubulin incorporated into axonemes (cilia and flagella). Both polyglutamylation and monoglycylation can coexist on the same protein on adjacent residues, and lowering glycylation levels increases polyglutamylation, and reciprocally. The precise function of monoglycylation is still unclear (Probable).; Phosphorylated on Ser-172 by CDK1 during the cell cycle, from metaphase to telophase, but not in interphase. This phosphorylation inhibits tubulin incorporation into microtubules.

Subcellular Location

Cytoplasm , cytoskeleton.

UNIPROT

SwissProt: Q13509 Human

Synonyms