Mechanisms and consequences of dysregulation of the Tiam family of Rac activators in disease

Biochem Soc Trans. 2020 Dec 18;48(6):2703-2719. doi: 10.1042/BST20200481.

Abstract

The Tiam family proteins - Tiam1 and Tiam2/STEF - are Rac1-specific Guanine Nucleotide Exchange Factors (GEFs) with important functions in epithelial, neuronal, immune and other cell types. Tiam GEFs regulate cellular migration, proliferation and survival, mainly through activating and directing Rac1 signalling. Dysregulation of the Tiam GEFs is significantly associated with human diseases including cancer, immunological and neurological disorders. Uncovering the mechanisms and consequences of dysregulation is therefore imperative to improving the diagnosis and treatment of diseases. Here we compare and contrast the subcellular localisation and function of Tiam1 and Tiam2/STEF, and review the evidence for their dysregulation in disease.

Keywords: Rac; Tiam1/STEF; cancer; guanine nucleotide exchange factor; molecular basis of health and disease.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Cell Adhesion
  • Cell Movement
  • Cell Proliferation
  • Cell Survival
  • Guanine Nucleotide Exchange Factors / metabolism*
  • Humans
  • Immune System
  • Neoplasms / metabolism*
  • Nervous System Diseases / metabolism
  • Neurons / metabolism
  • Protein Domains
  • RNA Processing, Post-Transcriptional
  • Signal Transduction
  • T-Lymphoma Invasion and Metastasis-inducing Protein 1 / metabolism*
  • rac GTP-Binding Proteins / metabolism*
  • rac1 GTP-Binding Protein / metabolism

Substances

  • Guanine Nucleotide Exchange Factors
  • T-Lymphoma Invasion and Metastasis-inducing Protein 1
  • TIAM1 protein, human
  • TIAM2 protein, human
  • rac GTP-Binding Proteins
  • rac1 GTP-Binding Protein