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Regulation of WASH-dependent actin polymerization and protein trafficking by ubiquitination.

Cell | Feb 28, 2013

http://www.ncbi.nlm.nih.gov/pubmed/23452853

Endosomal protein trafficking is an essential cellular process that is deregulated in several diseases and targeted by pathogens. Here, we describe a role for ubiquitination in this process. We find that the E3 RING ubiquitin ligase, MAGE-L2-TRIM27, localizes to endosomes through interactions with the retromer complex. Knockdown of MAGE-L2-TRIM27 or the Ube2O E2 ubiquitin-conjugating enzyme significantly impaired retromer-mediated transport. We further demonstrate that MAGE-L2-TRIM27 ubiquitin ligase activity is required for nucleation of endosomal F-actin by the WASH regulatory complex, a known regulator of retromer-mediated transport. Mechanistic studies showed that MAGE-L2-TRIM27 facilitates K63-linked ubiquitination of WASH K220. Significantly, disruption of WASH ubiquitination impaired endosomal F-actin nucleation and retromer-dependent transport. These findings provide a cellular and molecular function for MAGE-L2-TRIM27 in retrograde transport, including an unappreciated role of K63-linked ubiquitination and identification of an activating signal of the WASH regulatory complex.

Pubmed ID: 23452853 RIS Download

Mesh terms: Actins | DNA-Binding Proteins | Endosomes | Gene Knockdown Techniques | Golgi Apparatus | Humans | Microfilament Proteins | Multiprotein Complexes | Nuclear Proteins | Protein Transport | Proteins | RNA Interference | Ubiquitin-Conjugating Enzymes | Ubiquitination

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Associated grants

  • Agency: NCI NIH HHS, Id: CA110261
  • Agency: NIAID NIH HHS, Id: R01 AI065474
  • Agency: NIGMS NIH HHS, Id: R01 GM056322
  • Agency: NIGMS NIH HHS, Id: R01 GM063692
  • Agency: NIAID NIH HHS, Id: R01-AI065474
  • Agency: NIGMS NIH HHS, Id: R01-GM063692
  • Agency: NIGMS NIH HHS, Id: R01-GM56322
  • Agency: Howard Hughes Medical Institute, Id:
  • Agency: Howard Hughes Medical Institute, Id:

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