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Double donut versus filament: How structural shapes regulate SPOP activity and cancer pathogenesis

Lorraine Glennie1, Danny T Huang2

  • 1Cancer Research UK Scotland Institute, Garscube Estate, Switchback Road, Glasgow G61 1BD, UK.

Molecular Cell
|August 6, 2026
PubMed

Insights

The study reveals Scaffold Protein (SPOP) exists in two states: inactive double donuts and active linear filaments. This equilibrium disruption is linked to cancer development.

Area of Science:

  • Biochemistry
  • Molecular Biology
  • Cancer Biology

Background:

  • Scaffold Protein (SPOP) is a key protein involved in cellular processes.
  • Dysregulation of SPOP has been implicated in various cancers.

Purpose of the Study:

  • To investigate the quaternary states of SPOP.
  • To understand how SPOP states are regulated and their role in cancer.

Main Methods:

  • Structural biology techniques to visualize SPOP oligomers.
  • Biochemical assays to study SPOP state transitions.

Main Results:

  • SPOP exists in an equilibrium between two quaternary states: inactive double donuts and active linear filaments.
  • Gain-of-function cancer mutations are associated with specific SPOP oligomeric states.

Conclusions:

  • The equilibrium between SPOP quaternary states is crucial for normal cellular function.
  • Dysregulation of this SPOP equilibrium contributes to cancer pathogenesis.

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