Protein kinase Cdelta (PKCdelta) has been implicated both as a tumor suppressor and a positive regulator of cell cycle progression. PKCdelta has also been reported to positively and negatively regulate apoptotic programs. This has led to conflicting hypotheses on the role of PKCdelta in the control of cell proliferation and survival. Surprisingly, PKCdelta mice develop normally and are fertile, indicating that PKCdelta is not critical for normal cell proliferation during development. However, PKCdelta may play important roles in neoplastic cell proliferation. In this review, we have summarized the apparent multifunctional properties of this enigmatic protein with regard to its role in the regulation of cell cycle progression and cell survival. It is proposed that PKCdelta has both tumor suppressor and proliferation capabilities that can be recruited as a backup kinase for both gatekeeper tumor suppression and as an activator of the Ras/Raf/MEK/MAP kinase signaling pathway in cell proliferation.
Cellular aggregation is an essential step in the formation of biofilms, which promote fungal survival and persistence in hosts. In many of the known yeast cell adhesion proteins, there are amino acid sequences predicted to form amyloid-like β-aggregates. These sequences mediate amyloid formation , these sequences mediate a phase transition from a disordered state to a partially ordered state to create patches of adhesins on the cell surface. These β-aggregated protein patches are called adhesin nanodomains, and their presence greatly increases and strengthens cell-cell interactions in fungal cell aggregation. Nanodomain formation is slow (with molecular response in minutes and the consequences being evident for hours), and strong interactions lead to enhanced biofilm formation. Unique among functional amyloids, fungal adhesin β-aggregation can be triggered by the application of physical shear force, leading to cellular responses to flow-induced stress and the formation of robust biofilms that persist under flow. Bioinformatics analysis suggests that this phenomenon may be widespread. Analysis of fungal abscesses shows the presence of surface amyloids, a finding which supports the idea that phase changes to an amyloid-like state occur . The amyloid-coated fungi bind the damage-associated molecular pattern receptor serum amyloid P component, and there may be a consequential modulation of innate immune responses to the fungi. Structural data now suggest mechanisms for the force-mediated induction of the phase change. We summarize and discuss evidence that the sequences function as triggers for protein aggregation and subsequent cellular aggregation, both and .
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