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XK-related protein 5 (XKR5) is a novel negative regulator of KIT/D816V-mediated transformation

Jianmin Sun1,2,3, Tine Thingholm2,3,4, Peter Højrup4

  • 1Department of Pathogen Biology and Immunology, School of Basic Medical Sciences, Ningxia Medical University, Yinchuan, China.

Oncogenesis
|June 19, 2018
PubMed

Insights

Researchers identified XKR5 as a novel negative regulator of KIT-mediated transformation. This protein, XKR5 (XK-related protein 5), phosphorylates and downregulates oncogenic KIT signaling, reducing cell proliferation.

Area of Science:

  • Molecular Biology
  • Oncology
  • Cell Signaling

Background:

  • Oncogenic KIT mutations, like KIT/D816V, drive cellular transformation.
  • Understanding the molecular mediators of KIT-driven transformation is crucial for therapeutic development.

Purpose of the Study:

  • To investigate the molecular mechanisms underlying KIT/D816V-induced cellular transformation.
  • To identify proteins that selectively interact with KIT/D816V and mediate its oncogenic effects.

Main Methods:

  • Mass spectrometry was employed to identify proteins binding to KIT/D816V.
  • Co-immunoprecipitation and Western blotting were used to confirm interactions and phosphorylation events.
  • Cell proliferation and colony formation assays assessed the functional impact of XKR5.

Main Results:

  • XKR5 (XK-related protein 5) was identified as a novel interacting protein with KIT/D816V.
  • XKR5 undergoes tyrosine phosphorylation upon interaction with KIT/D816V.
  • Phosphorylated XKR5 negatively regulates KIT signaling, downregulating ERK, AKT, and p38 phosphorylation, thereby reducing cell proliferation and colony formation.

Conclusions:

  • XKR5 acts as a novel negative regulator of KIT-mediated transformation.
  • The interaction between XKR5 and KIT/D816V provides new insights into controlling oncogenic KIT signaling.

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