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NUDT21 Drives T-Cell Acute Lymphoblastic Leukemia Through Dual Regulation of Alternative Polyadenylation and Transcriptional Activation - PubMed

5 hours ago
  • #T-ALL
  • #NUDT21
  • #Oncogenic Regulation
  • NUDT21 is identified as a key factor in T-ALL maintenance, upregulated in patients and linked to poor outcomes.
  • Mechanistically, NUDT21 promotes distal poly(A) site usage for oncogenic transcripts like UBE2D3, enhancing mRNA stability and protein expression, which drives proliferation via MYC signaling.
  • NUDT21 also localizes to promoters, interacting with transcription factors (MYB, RUNX1, GATA3) to facilitate MYC transcription, extending its role beyond APA regulation.
  • Pharmacological targeting with ouabain octahydrate induces apoptosis in T-ALL cells by degrading NUDT21 and suppressing UBE2D3 and MYC, highlighting it as a therapeutic target.