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The NF-Y/p53 liaison: well beyond repression

Carol Imbriano1, Nerina Gnesutta, Roberto Mantovani

  • 1Dipartimento di Biologia, Università degli Studi di Modena e Reggio Emilia, Via Campi 213/d, 41100 Modena, Italy.

Biochimica Et Biophysica Acta
|December 6, 2011
PubMed

Insights

The transcription factor NF-Y interacts with p53, influencing cell survival and death pathways, particularly under DNA-damage conditions. This interaction is critical for regulating gene expression and cellular responses to stress.

Area of Science:

  • Molecular Biology
  • Cancer Research
  • Cellular Signaling

Background:

  • NF-Y is a transcription factor that binds to the CCAAT promoter element.
  • p53 is a key transcription factor regulating cellular responses to DNA damage and genomic instability, frequently altered in cancer.
  • The interplay between NF-Y and p53 (and related proteins p63, p73) impacts gene expression under DNA-damage conditions.

Purpose of the Study:

  • To elucidate the role of the NF-Y/p53 interaction in cellular fate determination.
  • To investigate how DNA damage and specific p53 mutations affect this interaction and downstream gene regulation.
  • To explore the involvement of NF-Y in pro-apoptotic activities, including mediation of p53 transcriptional activation and regulation by non-coding RNA PANDA.

Main Methods:

  • Analysis of transcriptional repression of NF-Y target genes under DNA-damage conditions.
  • Investigation of NF-Y's direct and indirect roles in apoptosis.
  • Examination of interactions between NF-Y, p53, p63, p73, TopBP1, and PANDA in various cellular contexts, including those with mutant p53.

Main Results:

  • The NF-Y/p53 interaction mediates transcriptional repression of specific genes in response to DNA damage.
  • NF-Y participates in pro-apoptotic functions, either through p53 activation or via regulation by PANDA.
  • Gain-of-function mutant p53, interacting with TopBP1, alters the cellular response, subverting normal NF-Y/p53 pathway functions.

Conclusions:

  • The intricate connection between p53 and NF-Y is a critical determinant of cell survival versus cell death.
  • Dysregulation of the NF-Y/p53 axis, particularly in the context of mutant p53 and DNA repair proteins, has significant implications for cancer.
  • Understanding these molecular interactions provides insights into therapeutic strategies targeting cancer cell fate.

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