We found a match
Your institution may have access to this item. Find your institution then sign in to continue.
- Title
PARP1 negatively regulates MAPK signaling by impairing BRAF-X1 translation.
- Authors
Marranci, Andrea; Prantera, Antonella; Masotti, Simona; De Paolo, Raffaella; Baldanzi, Caterina; Podda, Maurizio S.; Mero, Serena; Vitiello, Marianna; Franchin, Cinzia; Laezza, Mariavittoria; Comelli, Laura; Arrigoni, Giorgio; Cervelli, Tiziana; Del Pozzo, Giovanna; Poliseno, Laura
- Abstract
In human cells BRAF oncogene is invariably expressed as a mix of two coding transcripts: BRAF-ref and BRAF-X1. These two mRNA isoforms, remarkably different in the sequence and length of their 3′UTRs, are potentially involved in distinct post-transcriptional regulatory circuits. Herein, we identify PARP1 among the mRNA Binding Proteins that specifically target the X1 3′UTR in melanoma cells. Mechanistically, PARP1 Zinc Finger domain down-regulates BRAF expression at the translational level. As a consequence, it exerts a negative impact on MAPK pathway, and sensitizes melanoma cells to BRAF and MEK inhibitors, both in vitro and in vivo. In summary, our study unveils PARP1 as a negative regulator of the highly oncogenic MAPK pathway in melanoma, through the modulation of BRAF-X1 expression.
- Subjects
MITOGEN-activated protein kinases; ZINC-finger proteins; CARRIER proteins; BRAF genes
- Publication
Journal of Hematology & Oncology, 2023, Vol 16, Issue 1, p1
- ISSN
1756-8722
- Publication type
Article
- DOI
10.1186/s13045-023-01428-2