title: PLK2 phosphorylates and inhibits enriched TAp73 in human osteosarcoma cells.
abstract: 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.
authors.affiliation: Department of Orthopedics, Zhu Jiang Hospital of Southern Medical University, Guangzhou, Guangdong, 510280, China.
authors.forename: Zheng Bo
authors.initials: ZB
authors.lastname: Hu
authors.affiliation: The State Key Laboratory of Respiratory Diseases, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou, Guangdong, 510280, China.
authors.forename: Xiao Hong
authors.initials: XH
authors.lastname: Liao
authors.affiliation: Department of Orthopedics, Zhu Jiang Hospital of Southern Medical University, Guangzhou, Guangdong, 510280, China.
authors.forename: Zun Ying
authors.initials: ZY
authors.lastname: Xu
authors.affiliation: Department of Orthopedics, Zhu Jiang Hospital of Southern Medical University, Guangzhou, Guangdong, 510280, China.
authors.forename: Xiao
authors.initials: X
authors.lastname: Yang
authors.affiliation: Department of Orthopedics, Zhu Jiang Hospital of Southern Medical University, Guangzhou, Guangdong, 510280, China.
authors.forename: Chao
authors.initials: C
authors.lastname: Dong
authors.affiliation: Department of Orthopedics, Zhu Jiang Hospital of Southern Medical University, Guangzhou, Guangdong, 510280, China.
authors.forename: An Min
authors.initials: AM
authors.lastname: Jin
authors.affiliation: Department of Orthopaedics, The Third Affiliated Hospital of Southern Medical University, Academy of Orthopedics, Guangzhou, Guangdong, 510665, China.
authors.forename: Hai
authors.initials: H
authors.lastname: Lu
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects; D001859:Bone Neoplasms / Q000235:genetics / Q000378:metabolism*; D002384:Catalysis; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects / Q000235:genetics; D049109:Cell Proliferation / Q000187:drug effects; D002945:Cisplatin / Q000494:pharmacology; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D059585:G1 Phase Cell Cycle Checkpoints; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D055786:Gene Knockout Techniques; D006801:Humans; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism*; D012516:Osteosarcoma / Q000235:genetics / Q000378:metabolism*; D010766:Phosphorylation; D011485:Protein Binding; D011499:Protein Processing, Post-Translational; D017346:Protein Serine-Threonine Kinases / Q000235:genetics / Q000378:metabolism*; D014158:Transcription, Genetic; D000072160:Tumor Protein p73; D025521:Tumor Suppressor Proteins / Q000235:genetics / Q000378:metabolism*
chemical_list: D000970:Antineoplastic Agents; D004268:DNA-Binding Proteins; D009687:Nuclear Proteins; D000072160:Tumor Protein p73; D025521:Tumor Suppressor Proteins; C496126:PLK2 protein, human; D017346:Protein Serine-Threonine Kinases; D002945:Cisplatin
keywords: Antitumor; PLK2; TAp73; cisplatin; phosphorylation