TY - JOUR TI - Gfi1 upregulates c-Myc expression and promotes c-Myc-driven cell proliferation AU - Zhang, Yangyang AU - Dong, Fan T2 - Scientific Reports AB - 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. DA - 2020/10/13/ PY - 2020 DO - 10.1038/s41598-020-74278-4 DP - www.nature.com VL - 10 IS - 1 SP - 17115 LA - en SN - 2045-2322 UR - https://www.nature.com/articles/s41598-020-74278-4 Y2 - 2020/10/13/22:30:18 ER -