Transcription Factor NFAT1 Activates the mdm2 Oncogene Independent of p53

Abstract

Background: Mdm2 oncogene expression is regulated by p53-dependent and -independent mechanisms. Results: The NFAT1 transcription factor binds to the mdm2 P2 promoter and transactivates mdm2 independent of p53. Conclusion: NFAT1 is a transcriptional activator of the mdm2 oncogene. Significance: The identification of p53-independent control of mdm2 expression by NFAT1 will increase the understanding of the roles of NFAT1 in cancer.

The Oncoprotein HBXIP Modulates the Feedback Loop of MDM2/p53 to Enhance the Growth of Breast Cancer

“…Thus, we identified that HBXIP could increase the ubiquitination levels of p53 and that the effect of HBXIP on p53 was attenuated by MDM2 siRNA in the cells. Many studies have demonstrated that the levels of p53 are decreased by a variety of oncoproteins through up-regulating MDM2 in cancers (57,58). Here we found that HBXIP enhanced the degradation of p53 through up-regulating MDM2.…”

Nuclear factor of activated T cells in cancer development and treatment

“…In NFAT1 and NFAT4 deficient mice, immune cells are resistant to activation-induced cell death, hyperactivation and defective Fas ligand production, highlighting their tumor suppressor activities [62,63]. However, NFAT1 has been shown to induce MDM2 transcription and inactivate p53 in breast cancer cells [64]. Baumgart et al previously report that NFAT1 expression correlates with advanced stage pancreatic cancer by silencing the tumor suppressor gene p15 [65].…”

MDM2, MDMX and p53 in oncogenesis and cancer therapy

“…For example, it will be interesting to determine the tissue-specific and stress-specific factors that control the expression of MDM2 from the P2 promoter. Originally identified as p53-responsive, it is now clear that other transcription factors can modulate expression from this promoter 30,31 .…”