Gfi1 upregulates c-Myc expression and promotes c-Myc-driven cell proliferation

Sci Rep. 2020 Oct 13;10(1):17115. doi: 10.1038/s41598-020-74278-4.


Gfi1 is a zinc-finger transcriptional repressor that plays an important role in hematopoiesis. When aberrantly activated, Gfi1 may function as a weak oncoprotein in the lymphoid system, but collaborates strongly with c-Myc in lymphomagenesis. The mechanism by which Gfi1 collaborates with c-Myc in lymphomagenesis is incompletely understood. We show here that Gfi1 augmented the expression of c-Myc protein in cells transfected with c-Myc expression constructs. The N-terminal SNAG domain and C-terminal ZF domains of Gfi1, but not its transcriptional repression and DNA binding activities, were required for c-Myc upregulation. We further show that Gfi1 overexpression led to reduced polyubiquitination and increased stability of c-Myc protein. Interestingly, the levels of endogenous c-Myc mRNA and protein were augmented upon Gfi1 overexpression, but reduced following Gfi1 knockdown or knockout, which was associated with a decline in the expression of c-Myc-activated target genes. Consistent with its role in the regulation of c-Myc expression, Gfi1 promoted Myc-driven cell cycle progression and proliferation. Together, these data reveal a novel mechanism by which Gfi1 augments the biological function of c-Myc and may have implications for understanding the functional collaboration between Gfi1 and c-Myc in lymphomagenesis.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Cell Line, Tumor
  • Cell Proliferation / genetics*
  • DNA-Binding Proteins / genetics
  • DNA-Binding Proteins / physiology*
  • Gene Expression Regulation, Neoplastic / genetics
  • HeLa Cells
  • Humans
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Proto-Oncogene Proteins c-myc / genetics
  • Proto-Oncogene Proteins c-myc / physiology*
  • Real-Time Polymerase Chain Reaction
  • Transcription Factors / genetics
  • Transcription Factors / physiology*
  • Up-Regulation


  • DNA-Binding Proteins
  • GFI1 protein, human
  • MYC protein, human
  • Proto-Oncogene Proteins c-myc
  • Transcription Factors