Journal of Microbiology and Biotechnology

The Korean Society for Microbiology and Biotechnology (한국미생물·생명공학회)
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Cullin 3/KCTD5 Promotes the Ubiqutination of Rho Guanine Nucleotide Dissociation Inhibitor 1 and Regulates Its Stability

  • Cho, Hee Jun (Immunotherapy Research Center, Korea Research Institute of Bioscience and Biotechnology (KRIBB)) ;
  • Ryu, Ki-Jun (Division of Applied Life Science, Research Institute of Life Sciences, Gyeongsang National University) ;
  • Baek, Kyoung Eun (Immunotherapy Research Center, Korea Research Institute of Bioscience and Biotechnology (KRIBB)) ;
  • Lim, Jeewon (Immunotherapy Research Center, Korea Research Institute of Bioscience and Biotechnology (KRIBB)) ;
  • Kim, Taeyoung (Division of Applied Life Science, Research Institute of Life Sciences, Gyeongsang National University) ;
  • Song, Chae Yeong (Division of Applied Life Science, Research Institute of Life Sciences, Gyeongsang National University) ;
  • Yoo, Jiyun (Division of Applied Life Science, Research Institute of Life Sciences, Gyeongsang National University) ;
  • Lee, Hee Gu (Immunotherapy Research Center, Korea Research Institute of Bioscience and Biotechnology (KRIBB))
  • Received : 2020.07.24
  • Accepted : 2020.08.26
  • Published : 2020.10.28
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Abstract

Rho guanine nucleotide dissociation inhibitor 1 (RhoGDI1) plays important roles in numerous cellular processes, including cell motility, adhesion, and proliferation, by regulating the activity of Rho GTPases. Its expression is altered in various human cancers and is associated with malignant progression. Here, we show that RhoGDI1 interacts with Cullin 3 (CUL3), a scaffold protein for E3 ubiquitin ligase complexes. Ectopic expression of CUL3 increases the ubiquitination of RhoGDI1. Furthermore, potassium channel tetramerization domain containing 5 (KCTD5) also binds to RhoGDI1 and increases its interaction with CUL3. Ectopic expression of KCTD5 increases the ubiquitination of RhoGDI1, whereas its knockdown by RNA interference has the opposite effect. Depletion of KCTD5 or expression of dominant-negative CUL3 (DN-CUL3) enhances the stability of RhoGDI1. Our findings reveal a previously unknown mechanism for controlling RhoGDI1 degradation that involves a CUL3/KCTD5 ubiquitin ligase complex.

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