Oncogenic nature of a novel mutant AATF and its interactome existing within human cancer cells

Cell Biol Int. 2015 Mar;39(3):326-33. doi: 10.1002/cbin.10379. Epub 2014 Sep 26.

Abstract

Since apoptosis presents a natural defense in cancer development, the anti-apoptotic factor AATF/Che-1 has emerged as a crucial 'Epigenomic-Switch'. We have tried to understand the double-edged nature of AATF, showing for the first time the conspicuous existence of an aberrant AATF/Che-1 transcriptome encoding for 23 kDa mutant AATF protein, which evolves its unique interactome within human cancer cells derived from different tissue origins. This mutant AATF along with its interactome consisting of SP1, DNMT3B and Par-4 ensures cancer cell DNA methylation required for down-regulation of tumor suppressor genes. Hence, the proposed mutant AATF interactome-based pathway can have the inherent ability to ensure human cells become and remain cancerous.

Keywords: Cancer cells; DNMT3B; Mutant-AATF; Oncogenomics.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Apoptosis Regulatory Proteins / genetics*
  • Apoptosis Regulatory Proteins / metabolism*
  • Autophagy
  • Cell Line, Tumor
  • DNA (Cytosine-5-)-Methyltransferases / antagonists & inhibitors
  • DNA (Cytosine-5-)-Methyltransferases / genetics
  • DNA (Cytosine-5-)-Methyltransferases / metabolism
  • DNA Methylation
  • DNA Methyltransferase 3B
  • Down-Regulation
  • G1 Phase Cell Cycle Checkpoints
  • HeLa Cells
  • Humans
  • Jurkat Cells
  • Molecular Sequence Data
  • Mutation
  • Neoplasms / genetics*
  • Neoplasms / physiopathology
  • Promoter Regions, Genetic
  • RNA Interference
  • RNA, Small Interfering / metabolism
  • Repressor Proteins / genetics*
  • Repressor Proteins / metabolism*
  • Sp1 Transcription Factor / genetics
  • Sp1 Transcription Factor / metabolism

Substances

  • AATF protein, human
  • Apoptosis Regulatory Proteins
  • RNA, Small Interfering
  • Repressor Proteins
  • Sp1 Transcription Factor
  • prostate apoptosis response-4 protein
  • DNA (Cytosine-5-)-Methyltransferases