Related Experiment Video

Updated: Sep 5, 2025

Identification of Inositol Phosphate or Phosphoinositide Interacting Proteins by Affinity Chromatography Coupled to Western Blot or Mass Spectrometry
08:07

Identification of Inositol Phosphate or Phosphoinositide Interacting Proteins by Affinity Chromatography Coupled to Western Blot or Mass Spectrometry

Published on: July 26, 2019

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Hippo pathway regulation by phosphatidylinositol transfer protein and phosphoinositides

Fu-Long Li1,2, Vivian Fu1,2, Guangbo Liu1,2

  • 1Department of Pharmacology, University of California San Diego, La Jolla, CA, USA.

Nature Chemical Biology
|July 5, 2022
PubMed

Insights

Microcolin B activates the Hippo pathway, targeting YAP-dependent cancers. This study identifies phosphatidylinositol transfer proteins (PITPα/β) as key regulators, offering new therapeutic avenues for cancer treatment.

Area of Science:

  • Molecular Biology
  • Cell Biology
  • Biochemistry

Background:

  • The Hippo pathway regulates organ size and is crucial for tissue homeostasis.
  • Dysregulation of the Hippo pathway is implicated in cancer development.
  • LATS kinases inhibit YAP/TAZ co-activators, suppressing cell growth.

Purpose of the Study:

  • To identify novel Hippo pathway activators from marine natural products.
  • To elucidate the molecular targets and mechanisms of microcolin B (MCB).
  • To explore the role of identified targets in cancer therapy.

Main Methods:

  • Screening of marine natural products to identify Hippo pathway activators.
  • Structure-activity relationship studies of MCB analogs.
  • Biochemical assays to identify direct molecular targets.
  • Investigation of PITPα/β function in Hippo pathway regulation.

Main Results:

  • Microcolin B (MCB) was identified as a Hippo pathway activator that selectively kills YAP-dependent cancer cells.
  • Structure-activity optimization led to more potent MCB analogs.
  • Phosphatidylinositol transfer proteins α and β (PITPα/β) were identified as direct MCB targets.
  • PITPα/β were found to regulate LATS and YAP activity.
  • PITPα/β influence the Hippo pathway through plasma membrane phosphatidylinositol-4-phosphate.

Conclusions:

  • PITPα/β play a previously unrecognized role in regulating the Hippo pathway.
  • PITPα/β are potential therapeutic targets for cancer treatment.
  • MCB and its analogs represent promising leads for developing novel cancer therapies targeting the Hippo pathway.

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