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In Vitro SUMOylation Assay to Study SUMO E3 Ligase Activity
09:45

In Vitro SUMOylation Assay to Study SUMO E3 Ligase Activity

Published on: January 29, 2018

Pc2-mediated sumoylation of Smad-interacting protein 1 attenuates transcriptional repression of E-cadherin

Jianyin Long1, Dongmei Zuo, Morag Park

  • 1Molecular Oncology Group, McGill University, Montréal, Québec H3A 1A1, Canada.

The Journal of Biological Chemistry
|August 3, 2005
PubMed

Insights

Sumoylation of Smad-interacting protein 1 (SIP1) by Pc2 regulates its activity. This modification impacts E-cadherin repression, offering a potential target for cancer therapy.

Area of Science:

  • Molecular Biology
  • Cell Biology
  • Cancer Research

Background:

  • Epithelial-mesenchymal transition (EMT) is crucial for development and cancer.
  • Smad-interacting protein 1 (SIP1) induces EMT by repressing E-cadherin transcription via C-terminal-binding protein (CtBP).
  • Regulation of SIP1 activity remains largely unknown.

Purpose of the Study:

  • To investigate the regulation of SIP1 activity.
  • To identify post-translational modifications of SIP1.
  • To explore the role of SIP1 modification in EMT and tumorigenesis.

Main Methods:

  • In vivo and in vitro studies of SIP1.
  • Identification of sumoylation sites on SIP1 (Lys391 and Lys866).
  • Assays to determine the E3 ligase activity of Pc2 and PIAS proteins on SIP1.
  • Reporter gene assays to assess transcriptional activity.
  • Analysis of CtBP recruitment to SIP1.

Main Results:

  • SIP1 is sumoylated at Lys391 and Lys866 by the polycomb protein Pc2.
  • Sumoylation does not alter SIP1 localization but regulates its transcriptional activity.
  • A sumoylation-null SIP1 mutant shows enhanced repression of E-cadherin transcription.
  • SIP1 sumoylation disrupts CtBP recruitment, affecting promoter-specific activity.

Conclusions:

  • SIP1 sumoylation by Pc2 is a key regulatory mechanism.
  • This modification modulates SIP1's transcriptional activity in a context-dependent manner.
  • SIP1 sumoylation represents a potential therapeutic target for modulating EMT in cancer.

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