p73-mediated transcriptional activity is negatively regulated by polo-like kinase 1.
Trans-activating (TA) p73 is a member of the p53 family of transcription factors and has been implicated in cell cycle regulation, apoptosis and developmental processes. Although TAp73 positively regulates an overlapping repertoire of genes regulated by p53, TAp73 has been observed to be paradoxically overexpressed in a number of tumor cell types arousing much interest in the post-translational regulation of TAp73 transcriptional activity. Here, we present novel findings that show TAp73 can interact and co-localise, with Polo-Like Kinase 1 (PLK1) and that TAp73 is phosphorylated by this kinase on Threonine-27 (Thr-27) within the TA domain. Using reporter assays and Electrophoretic Mobility Shift Assays (EMSA), our findings suggest that TAp73-mediated activation of the p21(cip/waf), 14-3-3sigma and Bax gene promoters is abrogated by expressed PLK1 for which post-translational modification of TAp73 Thr-27 appears to be a key step in MCF7 cells. Thus highlighting a potential mechanism that uniquely contributes to PLK1-mediated and phosphor-dependent transcriptional deactivation of expressed TAp73.
Soond
Surinder M
SM
Medical Molecular Biology Unit, Institute of Child Health, University College London, London, United Kingdom. s.soond@ich.ucl.ac.uk
Barry
Sean P
SP
Melino
Gerry
G
Knight
Richard A
RA
Latchman
David S
DS
Stephanou
Anastasis
A
D000595:Amino Acid Sequence / Q000235:genetics; D051017:Apoptosis Regulatory Proteins / Q000235:genetics / Q000378:metabolism; D001665:Binding Sites / Q000235:genetics; D018797:Cell Cycle Proteins / Q000235:genetics* / Q000378:metabolism; D002471:Cell Transformation, Neoplastic / Q000235:genetics* / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism; D015536:Down-Regulation / Q000235:genetics; D015972:Gene Expression Regulation, Neoplastic / Q000235:genetics; D006801:Humans; D009687:Nuclear Proteins / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism; D010766:Phosphorylation; D011401:Promoter Regions, Genetic / Q000235:genetics; D011499:Protein Processing, Post-Translational / Q000235:genetics*; D017346:Protein Serine-Threonine Kinases / Q000235:genetics* / Q000378:metabolism; D011518:Proto-Oncogene Proteins / Q000235:genetics* / Q000378:metabolism; D013912:Threonine / Q000378:metabolism; D015533:Transcriptional Activation / Q000235:genetics*; D014407:Tumor Cells, Cultured; D000072160:Tumor Protein p73; D025521:Tumor Suppressor Proteins / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism; D000097869:Polo-Like Kinase 1
D051017:Apoptosis Regulatory Proteins; D018797:Cell Cycle Proteins; D004268:DNA-Binding Proteins; D009687:Nuclear Proteins; D017346:Protein Serine-Threonine Kinases; D011518:Proto-Oncogene Proteins; D013912:Threonine; D000072160:Tumor Protein p73; D025521:Tumor Suppressor Proteins; D000097869:Polo-Like Kinase 1; C000606460:TP73 protein, human