Related Experiment Video

Updated: Aug 4, 2025

Characterize Disease-related Mutants of RAF Family Kinases by Using a Set of Practical and Feasible Methods
07:49

Characterize Disease-related Mutants of RAF Family Kinases by Using a Set of Practical and Feasible Methods

Published on: July 17, 2019

6.1K

PARP1 negatively regulates MAPK signaling by impairing BRAF-X1 translation

Andrea Marranci1,2,3, Antonella Prantera4,5,6, Simona Masotti4,5

  • 1Institute of Clinical Physiology (IFC), CNR, Via Moruzzi 1, 56124, Pisa, Italy. andrea.marranci@gmail.com.

Journal of Hematology & Oncology
|April 4, 2023
PubMed

Insights

Poly(ADP-ribose) polymerase 1 (PARP1) negatively regulates the BRAF oncogene in melanoma by targeting the BRAF-X1 transcript. This finding sensitizes melanoma cells to targeted therapies by impacting the MAPK pathway.

Area of Science:

  • Molecular Biology
  • Oncology
  • Gene Regulation

Background:

  • The BRAF oncogene is expressed as two main transcripts, BRAF-ref and BRAF-X1, with distinct 3'UTRs.
  • These isoforms may participate in different post-transcriptional regulatory mechanisms.

Discussion:

  • PARP1 specifically binds to the 3'UTR of the BRAF-X1 transcript in melanoma cells.
  • The Zinc Finger domain of PARP1 down-regulates BRAF expression at the translational level.

Key Insights:

  • PARP1 acts as a negative regulator of the MAPK pathway in melanoma.
  • PARP1 targeting of BRAF-X1 sensitizes melanoma cells to BRAF and MEK inhibitors in vitro and in vivo.

Outlook:

  • PARP1 represents a potential therapeutic target for melanoma treatment.
  • Further investigation into PARP1-mediated regulation of BRAF could reveal new therapeutic strategies.
Keywords:
BRAF-X1MAPK pathwayMelanomaPARP1VemurafenibmRBP

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