p90RSK Regulates p53 Pathway by MDM2 Phosphorylation in Thyroid Tumors

Résumé fourni par la source

Simple Summary: p90RSK is a downstream effector protein of the MAPK pathway.In many human cancers, the MAPK pathway is constitutively activated due to oncogenic mutations of its components.Consequently, p90RSK is hyperactive and capable of hyper phosphorylating substrates involved in tumorigenesis.p90RSK belongs to the AGC-kinase family, that phosphorylates substrates with RXRXXS/T consensus motif.MDM2 protein presents this consensus in its sequence, at serine 166.MDM2 is a ubiquitin-ligase that negatively regulates the protein stability of p53.The aim of this study has been to verify whether p90RSK is capable of phosphorylating MDM2 in serine 166 and to investigate the role of p90RSK in regulating the p53 pathway, especially in thyroid tumors in which the MAPK pathway is constitutively active and in which the development of specific drugs aimed at inhibiting the kinase activity of p90RSK could represent a new way to inhibit tumorigenesis.

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