PLK2 phosphorylates and inhibits enriched TAp73 in human osteosarcoma cells.
TAp73, a member of the p53 tumor suppressor family, can substitute for p53 function, especially in p53-null and p53-mutant cells. However, TAp73 enrichment and phosphorylation change its transcriptional activity. Previously, we found that the antitumor function of TAp73 was reactivated by dephosphorylation. Polo-like kinase 2 (PLK2) plays an important role in bone development. Using a biological information database and phosphorylation prediction software, we hypothesized that PLK2 phosphorylates TAp73 and inhibits TAp73 function in osteosarcomas. Actually,we determined that PLK2 physically binds to and phosphorylates TAp73 when TAp73 protein abundance is up-regulated by cisplatin. PLK2-phosphorylated TAp73 at residue Ser48 within the TA domain; phosphorylation of TAp73 was abolished by mutating this residue. Moreover, PLK2 inhibition combined with cisplatin treatment in osteosarcoma Saos2 cells up-regulated p21 and puma mRNA expression to a greater extent than cisplatin treatment alone. Inhibiting PLK2 in TAp73-enriched Saos2 cells resulted in inhibited cell proliferation, increased apoptosis, G1 phase arrest, and decreased cell invasion. However, these changes did not occur in TAp73 knockdown Saos2 cells. In conclusion, these findings reveal a novel PLK2 function in the phosphorylation of TAp73, which prevents TAp73 activity in osteosarcoma cells. Thereby, this research provides an insight into the clinical treatment of malignant tumors overexpressing TAp73.
['Hu|Zheng Bo|ZB|', 'Liao|Xiao Hong|XH|', 'Xu|Zun Ying|ZY|', 'Yang|Xiao|X|', 'Dong|Chao|C|', 'Jin|An Min|AM|', 'Lu|Hai|H|']
D000970:Antineoplastic Agents D017209:Apoptosis D001859:Bone Neoplasms D002384:Catalysis D045744:Cell Line, Tumor D002465:Cell Movement D049109:Cell Proliferation D002945:Cisplatin D004268:DNA-Binding Proteins D059585:G1 Phase Cell Cycle Checkpoints D015972:Gene Expression Regulation, Neoplastic D055786:Gene Knockout Techniques D006801:Humans D009687:Nuclear Proteins D012516:Osteosarcoma D010766:Phosphorylation D011485:Protein Binding D011499:Protein Processing, Post-Translational D017346:Protein Serine-Threonine Kinases D014158:Transcription, Genetic D000072160:Tumor Protein p73 D025521:Tumor Suppressor Proteins
PLK2 phosphorylation TAp73 Antitumor cisplatin