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Targeting the Y/CCAAT box in cancer: YB-1 (YBX1) or NF-Y?

D Dolfini1, R Mantovani

  • 1Dipartimento di Bioscienze, Università degli Studi di Milano, Via Celoria 26, Milan 20133, Italy.

Cell Death and Differentiation
|March 2, 2013
PubMed

Insights

Nuclear factor Y (NF-Y) and Y box-binding protein 1 (YB-1) are key transcription factors regulating genes in cancer. These factors are crucial for cancer cell growth and drug resistance, impacting numerous growth-related genes.

Area of Science:

  • Molecular Biology
  • Cancer Biology
  • Genetics

Background:

  • The Y box, a CCAAT box-containing motif, is enriched in promoters of cancer-overexpressed genes.
  • Transcription factors Nuclear Factor Y (NF-Y) and Y box-binding protein 1 (YB-1) interact with the Y box.
  • YB-1 is an oncogene overexpressed in aggressive tumors and linked to drug resistance.

Purpose of the Study:

  • To review two decades of data on NF-Y and YB-1's roles in cancer.
  • To highlight their involvement in Y/CCAAT-dependent gene activation.
  • To emphasize YB-1's additional roles in post-transcriptional mRNA control in cancer.

Main Methods:

  • Biochemical purification of NF-Y heterotrimer.
  • Screening of expression libraries for YB-1 cloning.
  • Review of existing scientific literature and genome-wide data.

Main Results:

  • NF-Y and YB-1 are critical for activating growth-related genes in cancer cells, including multidrug resistance protein 1.
  • Genome-wide data confirm NF-Y's action on Y/CCAAT sequences in cancer.
  • YB-1 possesses functions beyond DNA binding, affecting mRNA biology.

Conclusions:

  • NF-Y is a primary factor acting on Y/CCAAT in cancer cells.
  • YB-1 is a significant oncogene with multifaceted roles in cancer biology, including drug resistance.
  • Both NF-Y and YB-1 are crucial targets for understanding and potentially treating cancer.

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