Accumulated SET protein up-regulates and interacts with hnRNPK, increasing its binding to nucleic acids, the Bcl-xS repression, and cellular proliferation

Author(s)

Almeida, Luciana O. ^[1] ; Garcia, Cristiana B. ^[1] ; Matos-Silva, Flavia A. ^[1] ; Curti, Carlos ^[2] ; Leopoldino, Andreia M. ^[1]

Affiliation

^[1] Univ Sao Paulo, Sch Pharmaceut Sci Ribeirao Preto, Dept Clin Anal Toxicol & Food Sci, BR-14040903 Ribeirao Preto, SP - Brazil

^[2] Univ Sao Paulo, Sch Pharmaceut Sci Ribeirao Preto, Dept Chem & Phys, BR-14040903 Ribeirao Preto, SP - Brazil

• Document type: Journal article
• Source: Biochemical and Biophysical Research Communications; v. 445, n. 1, p. 196-202, FEB 28 2014.
• Web of Science Citations: 9

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. (C) 2014 Elsevier Inc. All rights reserved. (AU)

• FAPESP's process: 07/02223-6 - Study of proteins selected as potencial markers in head and neck cancer
• Grantee: Flávia Amoroso Matos e Silva
• Support Opportunities: Scholarships in Brazil - Master
• FAPESP's process: 09/52228-0 - Studies on resistance to apoptosis in cancer, head/neck model: signaling via with emphasis on PIP3-Akt/SET, oxidative stress, mitochondria and relationships
• Grantee: Carlos Curti
• Support Opportunities: Research Projects - Thematic Grants
• FAPESP's process: 09/10783-7 - Molecular study of hnRNP K and SET proteins on transcription and translational proteins associated in oral tumorigenesis
• Grantee: Luciana Oliveira de Almeida
• Support Opportunities: Scholarships in Brazil - Post-Doctoral
• FAPESP's process: 10/20384-0 - Identification of genes, miRNAs and proteins regulated by set oncoprotein and associated on malignization and tumor progression in HNSCC using in vitro and in vivo models
• Grantee: Andréia Machado Leopoldino
• Support Opportunities: Regular Research Grants
• FAPESP's process: 13/10898-4 - Study of the molecular mechanisms by protein SET with impact on tumorigenesis and progression of oral cancer
• Grantee: Carlos Curti
• Support Opportunities: Regular Research Grants