Hubbing the Cancer Cell.

Oncogenic transformation drives adaptive changes in a growing tumor that affect the cellular organization of cancerous cells, resulting in the loss of specialized cellular functions in the polarized compartmentalization of cells. The resulting altered metabolic and morphological patterns are used clinically as diagnostic markers. This review recapitulates the known functions of actin, microtubules and the γ-tubulin meshwork in orchestrating cell metabolism and functional cellular asymmetry.

The γ-tubulin meshwork assists in the recruitment of PCNA to chromatin in mammalian cells.

Changes in the location of γ-tubulin ensure cell survival and preserve genome integrity. We investigated whether the nuclear accumulation of γ-tubulin facilitates the transport of proliferating cell nuclear antigen (PCNA) between the cytosolic and the nuclear compartment in mammalian cells. We found that the γ-tubulin meshwork assists in the recruitment of PCNA to chromatin. Also, decreased levels of γ-tubulin reduce the nuclear pool of PCNA. In addition, the γ-tubulin C terminus encodes a PCNA-interacting peptide (PIP) motif, and a γ-tubulin-PIP-mutant affects the nuclear accumulation of PCNA. In a cell-free system, PCNA and γ-tubulin formed a complex. In tumors, there is a significant positive correlation between TUBG1 and PCNA expression. Thus, we report a novel mechanism that constitutes the basis for tumor growth by which the γ-tubulin meshwork maintains indefinite proliferation by acting as an opportune scaffold for the transport of PCNA from the cytosol to the chromatin.