RbAp48 is a Target of Nuclear Factor-κB Activity in Thyroid Cancer

Context: We have recently shown that nuclear factor (NF)-κB activity is constitutively elevated in anaplastic human thyroid carcinomas. The inhibition of NF-κB in the anaplastic thyroid carcinoma cell line (FRO) leads to increased susceptibility to apoptosis induced by chemotherapeutic drugs and to the block of oncogenic activity. Objectives: To understand better the molecular mechanisms played by NF-κB in thyroid oncogenesis, we performed a differential proteomic analysis between FRO transfected with a superrepressor form of inhibitor of κBα (IκBαM) and the parental counterpart (FRO Neo cells). Results: Differential proteomic analysis revealed that the retinoblastoma-associated protein 48 (RbAp48) is down-regulated in the absence of functional NF-κB. Immunohistochemical analysis of normal and pathological human thyroid specimens confirmed that RbAp48 is strongly overexpressed in primary human carcinomas. Reduction of RbAp48 expression using small interfering RNA determined the suppression of tumorigenici...

[1]  L. Montagnier,et al.  AGAR SUSPENSION CULTURE FOR THE SELECTIVE ASSAY OF CELLS TRANSFORMED BY POLYOMA VIRUS. , 1964, Virology.

[2]  J. Sambrook,et al.  Molecular Cloning: A Laboratory Manual , 2001 .

[3]  J. Fagin,et al.  High prevalence of mutations of the p53 gene in poorly differentiated human thyroid carcinomas. , 1993, The Journal of clinical investigation.

[4]  Y. Qian,et al.  A retinoblastoma-binding protein related to a negative regulator of Ras in yeast , 1993, Nature.

[5]  Jonathan Widom,et al.  The Major Cytoplasmic Histone Acetyltransferase in Yeast: Links to Chromatin Replication and Histone Metabolism , 1996, Cell.

[6]  A. Shevchenko,et al.  Mass spectrometric sequencing of proteins silver-stained polyacrylamide gels. , 1996, Analytical chemistry.

[7]  M. Pazin,et al.  What's Up and Down with Histone Deacetylation and Transcription? , 1997, Cell.

[8]  M J May,et al.  NF-kappa B and Rel proteins: evolutionarily conserved mediators of immune responses. , 1998, Annual review of immunology.

[9]  A. Bird,et al.  Analysis of the NuRD subunits reveals a histone deacetylase core complex and a connection with DNA methylation. , 1999, Genes & development.

[10]  H. Pahl.  Activators and target genes of Rel/NF-κB transcription factors , 1999, Oncogene.

[11]  M. Karin.  How NF-κB is activated: the role of the IκB kinase (IKK) complex , 1999, Oncogene.

[12]  M. Karin,et al.  Phosphorylation meets ubiquitination: the control of NF-[kappa]B activity. , 2000, Annual review of immunology.

[13]  B. Chait,et al.  ProFound: an expert system for protein identification using mass spectrometric peptide mapping information. , 2000, Analytical chemistry.

[14]  D. Hanahan,et al.  The Hallmarks of Cancer , 2000, Cell.

[15]  E. Nicolas,et al.  RbAp48 Belongs to the Histone Deacetylase Complex That Associates with the Retinoblastoma Protein* , 2000, The Journal of Biological Chemistry.

[16]  P. Tak,et al.  NF-κB: a key role in inflammatory diseases , 2001 .

[17]  T. Rudel,et al.  Predominant Identification of RNA-binding Proteins in Fas-induced Apoptosis by Proteome Analysis* , 2001, The Journal of Biological Chemistry.

[18]  E. Nicolas,et al.  The histone deacetylase HDAC3 targets RbAp48 to the retinoblastoma protein. , 2001, Nucleic acids research.

[19]  Francesca Zazzeroni,et al.  Induction of gadd45β by NF-κB downregulates pro-apoptotic JNK signalling , 2001, Nature.

[20]  Michael Karin,et al.  NF-κB in cancer: from innocent bystander to major culprit , 2002, Nature Reviews Cancer.

[21]  M. Vihinen,et al.  Changes in apoptosis-related pathways in acute myelocytic leukemia. , 2003, Cancer genetics and cytogenetics.

[22]  Osamu Iwasaki,et al.  Mis16 and Mis18 Are Required for CENP-A Loading and Histone Deacetylation at Centromeres , 2004, Cell.

[23]  Mu-jun Zhao,et al.  Genes encoding Pir51, Beclin 1, RbAp48 and aldolase b are up or down-regulated in human primary hepatocellular carcinoma. , 2004, World journal of gastroenterology.

[24]  G. Almouzni,et al.  Histone chaperones, a supporting role in the limelight. , 2004, Biochimica et biophysica acta.

[25]  M. Karin,et al.  The IKK/NF-κB activation pathway—a target for prevention and treatment of cancer , 2004 .

[26]  K. Buetow,et al.  Chromatin Remodeling Factors and BRM/BRG1 Expression as Prognostic Indicators in Non-Small Cell Lung Cancer , 2004, Clinical Cancer Research.

[27]  N. Dyson,et al.  p55, the Drosophila Ortholog of RbAp46/RbAp48, Is Required for the Repression of dE2F2/RBF-Regulated Genes , 2004, Molecular and Cellular Biology.

[28]  Michael Karin,et al.  IKKβ Links Inflammation and Tumorigenesis in a Mouse Model of Colitis-Associated Cancer , 2004, Cell.

[29]  Y. Ben-Neriah,et al.  NF-κB functions as a tumour promoter in inflammation-associated cancer , 2004, Nature.

[30]  A. Leonardi,et al.  Oncogenic and Anti-apoptotic Activity of NF-κB in Human Thyroid Carcinomas* , 2004, Journal of Biological Chemistry.

[31]  P. Marks,et al.  Novel Histone Deacetylase Inhibitors in the Treatment of Thyroid Cancer , 2005, Clinical Cancer Research.

[32]  Antonio Leonardi,et al.  ABIN-1 Binds to NEMO/IKKγ and Co-operates with A20 in Inhibiting NF-κB* , 2006, Journal of Biological Chemistry.

[33]  H. J. Kim,et al.  NF-κB and IKK as therapeutic targets in cancer , 2006, Cell Death and Differentiation.

[34]  A. Scaloni,et al.  Differential proteomic analysis of nuclear extracts from thyroid cell lines. , 2006, Journal of chromatography. B, Analytical technologies in the biomedical and life sciences.

[35]  O. Bosco,et al.  Valproic acid, a histone deacetylase inhibitor, enhances sensitivity to doxorubicin in anaplastic thyroid cancer cells. , 2006, The Journal of endocrinology.

[36]  A. Scaloni,et al.  Proteomic analysis of liver tissues subjected to early ischemia/reperfusion injury during human orthotopic liver transplantation , 2006, Proteomics.