Accumulated SET protein up-regulates and interacts with hnRNPK, increasing its binding to nucleic acids, the Bcl-xS repression, and cellular proliferation.
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.
['Almeida|Luciana O|LO|', 'Garcia|Cristiana B|CB|', 'Matos-Silva|Flavia A|FA|', 'Curti|Carlos|C|', 'Leopoldino|Andréia M|AM|']
D002294:Carcinoma, Squamous Cell D045744:Cell Line, Tumor D002467:Cell Nucleus D049109:Cell Proliferation D004268:DNA-Binding Proteins D005786:Gene Expression Regulation D057809:HEK293 Cells D006258:Head and Neck Neoplasms D034641:Heterogeneous-Nuclear Ribonucleoprotein K D056488:Histone Chaperones D006801:Humans D015151:Immunoblotting D018613:Microscopy, Confocal D009696:Nucleic Acids D010766:Phosphorylation D011485:Protein Binding D034622:RNA Interference D012333:RNA, Messenger D020133:Reverse Transcriptase Polymerase Chain Reaction D012261:Ribonucleoproteins D014157:Transcription Factors D015854:Up-Regulation D051020:bcl-X Protein
SET hnRNPK Bcl-xS HNSCC Alternative splicing Interaction DNA-protein SET–hnRNPK