title: Malignant genome reprogramming by ATAD2.
abstract: BACKGROUND
  Unscheduled expression of critical cellular regulators could be central to malignant genome reprogramming and tumor establishment. One such factor appears to be ATAD2, a remarkably conserved protein normally predominantly expressed in germ cells but almost systematically over-expressed in a variety of unrelated cancers. The presence of a bromodomain adjacent to an AAA type ATPase domain, points to ATAD2 as a factor preliminarily acting on chromatin structure and function. Accordingly, ATAD2 has been shown to cooperate with a series of transcription factors and chromatin modifiers to regulate specific set of genes.
  
  
  METHODS
  Here we discuss our knowledge on ATAD2 to evaluate its role as a cancer driver and its value as a new anti-cancer target.
  
  
  CONCLUSIONS
  Upon its activation, ATAD2 through its interaction with defined transcription factors, initiates a loop of transcriptional stimulation of target genes, including ATAD2 itself, leading to enhanced cell proliferation and resistance to apoptosis in an ATAD2-dependent manner. Approaches aiming at neutralizing ATAD2 activity in cancer, including the use of small molecule inhibitors of its two "druggable" domains, AAA ATPase and bromodomain, could become part of a promising anti-cancer strategy.
authors.affiliation: INSERM, U823, Université Joseph Fourier - Grenoble 1, Institut Albert Bonniot, Grenoble, F-38700, France.
authors.forename: Fayçal
authors.initials: F
authors.lastname: Boussouar
authors.forename: Mahya
authors.initials: M
authors.lastname: Jamshidikia
authors.forename: Yuichi
authors.initials: Y
authors.lastname: Morozumi
authors.forename: Sophie
authors.initials: S
authors.lastname: Rousseaux
authors.forename: Saadi
authors.initials: S
authors.lastname: Khochbin
mesh_terms: D000074183:ATPases Associated with Diverse Cellular Activities; D000251:Adenosine Triphosphatases / Q000235:genetics*; D004268:DNA-Binding Proteins / Q000235:genetics*; D044127:Epigenesis, Genetic / Q000235:genetics*; D015894:Genome, Human; D006801:Humans; D009369:Neoplasms / Q000235:genetics*
chemical_list: D004268:DNA-Binding Proteins; D000251:Adenosine Triphosphatases; C544857:ATAD2 protein, human; D000074183:ATPases Associated with Diverse Cellular Activities
keywords: Bromodomain inhibitor; Cancer testis; Germline; H4K5ac; Myc