title: Accumulated SET protein up-regulates and interacts with hnRNPK, increasing its binding to nucleic acids, the Bcl-xS repression, and cellular proliferation.
abstract: SET and hnRNPK are proteins involved in gene expression and regulation of cellular signaling. We previously demonstrated that SET accumulates in head and neck squamous cell carcinoma (HNSCC); hnRNPK is a prognostic marker in cancer. Here, we postulate that SET and hnRNPK proteins interact to promote tumorigenesis. We performed studies in HEK293 and HNSCC (HN6, HN12, and HN13) cell lines with SET/hnRNPK overexpression and knockdown, respectively. We found that SET and/or hnRNPK protein accumulation increased cellular proliferation. SET accumulation up-regulated hnRNPK mRNA and total/phosphorylated protein, promoted hnRNPK nuclear location, and reduced Bcl-x mRNA levels. SET protein directly interacted with hnRNPK, increasing both its binding to nucleic acids and Bcl-xS repression. We propose that hnRNPK should be a new target of SET and that SET-hnRNPK interaction, in turn, has potential implications in cell survival and malignant transformation.
authors: Department of Clinical Analyses, Toxicology and Food Sciences, School of Pharmaceutical Sciences of Ribeirão Preto, University of São Paulo, Ribeirão Preto, SP, Brazil.
authors: Luciana O
authors: LO
authors: Almeida
authors: Department of Clinical Analyses, Toxicology and Food Sciences, School of Pharmaceutical Sciences of Ribeirão Preto, University of São Paulo, Ribeirão Preto, SP, Brazil.
authors: Cristiana B
authors: CB
authors: Garcia
authors: Department of Clinical Analyses, Toxicology and Food Sciences, School of Pharmaceutical Sciences of Ribeirão Preto, University of São Paulo, Ribeirão Preto, SP, Brazil.
authors: Flavia A
authors: FA
authors: Matos-Silva
authors: Department of Physics and Chemistry, School of Pharmaceutical Sciences of Ribeirão Preto, University of São Paulo, Ribeirão Preto, SP, Brazil.
authors: Carlos
authors: C
authors: Curti
authors: Department of Clinical Analyses, Toxicology and Food Sciences, School of Pharmaceutical Sciences of Ribeirão Preto, University of São Paulo, Ribeirão Preto, SP, Brazil. Electronic address: andreiaml@usp.br.
authors: Andréia M
authors: AM
authors: Leopoldino
mesh_terms: D002294:Carcinoma, Squamous Cell / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D045744:Cell Line, Tumor; D002467:Cell Nucleus / Q000378:metabolism; D049109:Cell Proliferation; D004268:DNA-Binding Proteins; D005786:Gene Expression Regulation; D057809:HEK293 Cells; D006258:Head and Neck Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D034641:Heterogeneous-Nuclear Ribonucleoprotein K; D056488:Histone Chaperones / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D015151:Immunoblotting; D018613:Microscopy, Confocal; D009696:Nucleic Acids / Q000235:genetics / Q000378:metabolism*; D010766:Phosphorylation; D011485:Protein Binding; D034622:RNA Interference; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012261:Ribonucleoproteins / Q000235:genetics / Q000378:metabolism*; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*; D015854:Up-Regulation; D051020:bcl-X Protein / Q000235:genetics / Q000378:metabolism*
chemical_list: C494811:BCL2L1 protein, human; D004268:DNA-Binding Proteins; D034641:Heterogeneous-Nuclear Ribonucleoprotein K; D056488:Histone Chaperones; D009696:Nucleic Acids; D012333:RNA, Messenger; D012261:Ribonucleoproteins; C513473:SET protein, human; D014157:Transcription Factors; D051020:bcl-X Protein; C072074:HNRNPK protein, human
keywords: Alternative splicing; Bcl-xS; HNSCC; Interaction DNA-protein; SET; SET–hnRNPK; hnRNPK