Anillin Recedes in p53-Dependent Senescence of Tumor Cells and Reappears in Cells Escaping from Senescence.

Abstract

Anillin is a protein whose most recognizable function is coordinating the spatial distribution of cytoskeletal proteins during the course of cytokinesis. Its level increases in many types of cancer, and therefore, it has been proposed as a prognostic marker for some of them. Anillin is detected in the cell nucleus but so far, its nuclear role has not been recognized. Our recent studies have shown that anillin gene expression and protein level decrease in normal senescent cells, which could be attributed to inhibition of proliferation. However, its presence in the nucleus of neurons, postmitotic cells, suggests functions other than regulation of cytokinesis. Some data indicate that anillin expression may be regulated by p53, a protein usually induced in cells undergoing senescence due to various stimuli. The presence of p53 binding sites in the upstream promoter region of the anillin gene was mainly shown in in silico studies, and, so far, few experimental data seem to confirm such regulation. This study aimed to test whether anillin level decreases in senescent cancer cells and whether this is due to regulation by p53. Using p53-proficient and p53-deficient cancer cells, we have shown that anillin levels decreased in cells whose senescence was p53-dependent. We also showed that in cells escaping senescence, anillin reappeared with proliferation resumption, which correlated with decreased p53 levels. Our results demonstrate the universality of anillin reduction during the course of senescence and show that p53 is a negative regulator of this protein.