Aurora A kinase interacts with and phosphorylates VHL protein

Abstract

Abstract:The serine/threonin kinase Aurora A is an oncoprotein, whereas von Hippel-Lindau protein (pVHL) is a tumor suppressor protein. Both proteins have the same localization during mitosis: in the mitotic spindle and the centrosome. These two proteins also have common functions, such as the regulation of the cell cycle, the stability of the mitotic spindle and both intervene in the functioning of centrosomes. In this study we have analyzed the interaction between Aurora A and pVHL with immunoprecipitation and in vitro phosphorylation experiments. We have confirmed that the immunoprecipitation of pVHL from Hek 293 cell extracts were coupled with Aurora A. In addition, the interaction between the two proteins has been tested by analyzing the phosphorylation of pVHL in vitro by Aurora A. The results revealed that pVHL was phosphorylated by Aurora A. In conclusion, the study demonstrated that Aurora A interacts with and phosphorylates pVHL. Given the role of these two proteins in cell division as well as their status in cancer, this interaction requires further investigation.

Aurora a Overexpression and pVHL Reduced Expression Are Correlated with a Bad Kidney Cancer Prognosis

“…Altogether, the expression levels of the oncoprotein Aurora A and tumor suppressor pVHL correlate in an opposite manner and one has to better investigate to which extent a high level of Aurora A expression associated to a reduction in pVHL expression could be considered as a molecular signature of a high TNM stage and of a bad prognosis. Considering, Aurora A /pVHL interaction [47,48], it could be assumed that the decrease of pVHL could lead or at least participate to Aurora A overexpression [18]. Based on such results and on the observations of the present paper, it could be proposed that absence of Aurora A protein associated to a strong expression of pVHL in clear cells kidney carcinoma are of good prognosis for the disease.…”

“…These studies included three parts and started with a study in bioinformatics where the interaction 'in silico' was predicted with strong probability, and then an 'in vitro' test using a recombinant protein was done and confirmed this interaction. Finally an 'in vivo' study with endogenous proteins on cell cultures comes to consolidate this hypothesis [47,48].…”

The pVHL neglected functions, a tale of hypoxia-dependent and -independent regulations in cancer

“…Of note, the binding does not require proline hydroxylation, while CDKN1b site-specific mutation associated with cancer is shown to modulate this novel interaction. The pVHL is also a substrate of different kinases [58][59][60][61][62] and the functional meaning of these modifications is only partially understood. Roe et al [60] reported that the phosphorylation of pVHL Ser111 by Chk2 (checkpoint kinase 2) enhances pVHL-mediated transactivation of p53 on DNA damage by recruiting p300 and Tip60 to the chromatin of p53 target genes.…”