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SKP2 regulates TERT independently of RUNX1/ETO in AML subtypes lacking the t(8,21) translocation via CDKN1B and RB

Adam Azlan1, Yaashini Rajasegaran1, Aliaa Arina Rosli1,2

  • 1Department of Biomedical Sciences, Advanced Medical and Dental Institute, Universiti Sains Malaysia, 13200, Bertam, Pulau Pinang, Malaysia.

Scientific Reports
|October 6, 2025
PubMed

Insights

Skp2 protein suppression reduces TERT levels in acute myeloid leukemia (AML) lacking the t(8;21) translocation. This occurs independently of RUNX1/ETO, impacting CDKN1B and RB phosphorylation.

Area of Science:

  • Oncology
  • Molecular Biology
  • Cellular Signaling

Background:

  • Skp2 (Skip protein 2) is crucial for cancer progression by degrading key proteins.
  • TERT (Telomerase Reverse Transcriptase) is vital for cancer cell immortality.
  • RUNX1/ETO fusion protein regulates TERT in t(8;21) AML.

Purpose of the Study:

  • To investigate the role of Skp2 in TERT modulation in non t(8;21) AML.
  • To elucidate the mechanism of Skp2-mediated TERT regulation independent of RUNX1/ETO.

Main Methods:

  • Utilized non t(8;21) AML cell lines.
  • Performed direct suppression of Skp2.
  • Analyzed protein levels of TERT, CDKN1B, RB, E2F1, FOXO3, and c-Myc.
  • Assessed MYC binding to the TERT promoter.

Main Results:

  • Direct Skp2 suppression led to TERT suppression and CDKN1B accumulation.
  • Skp2 suppression increased underphosphorylated RB levels; E2F1 levels remained unchanged.
  • Inverse correlation observed between FOXO3 (decreased) and c-Myc (increased) post Skp2 suppression.
  • No change in MYC binding to the TERT promoter despite increased c-Myc, indicating TERT suppression was independent of MYC.

Conclusions:

  • Skp2 regulates TERT levels in non t(8;21) AML independently of RUNX1/ETO.
  • The mechanism involves modulation of CDKN1B and RB phosphorylation states.
  • Skp2 is a potential therapeutic target for AML subtypes lacking the t(8;21) translocation.
Keywords:
Acute myeloid leukemia (AML)Non t(8,21) AMLSKP2T(8,21) AMLTERT

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