Dysregulation of Microtubule Nucleating Proteins in Cancer Cells

SIMPLE SUMMARY: The dysfunction of microtubule nucleation in cancer cells changes the overall cytoskeleton organization and cellular physiology. This review focuses on the dysregulation of the γ-tubulin ring complex (γ-TuRC) proteins that are essential for microtubule nucleation. Recent research on the high-resolution structure of γ-TuRC has brought new insight into the microtubule nucleation mechanism. We discuss the effect of γ-TuRC protein overexpression on cancer cell behavior and new drugs directed to γ-tubulin that may offer a viable alternative to microtubule-targeting agents currently used in cancer chemotherapy. ABSTRACT: In cells, microtubules typically nucleate from microtubule organizing centers, such as centrosomes. γ-Tubulin, which forms multiprotein complexes, is essential for nucleation. The γ-tubulin ring complex (γ-TuRC) is an efficient microtubule nucleator that requires additional centrosomal proteins for its activation and targeting. Evidence suggests that there is a dysfunction of centrosomal microtubule nucleation in cancer cells. Despite decades of molecular analysis of γ-TuRC and its interacting factors, the mechanisms of microtubule nucleation in normal and cancer cells remains obscure. Here, we review recent work on the high-resolution structure of γ-TuRC, which brings new insight into the mechanism of microtubule nucleation. We discuss the effects of γ-TuRC protein dysregulation on cancer cell behavior and new compounds targeting γ-tubulin. Drugs inhibiting γ-TuRC functions could represent an alternative to microtubule targeting agents in cancer chemotherapy.