Y-box protein-1 controls transforming growth factor-beta1 translation in proximal tubular cells

Kidney Int. 2008 Mar;73(6):724-32. doi: 10.1038/sj.ki.5002719. Epub 2007 Dec 12.


Transforming growth factor-beta1 (TGF-beta1) mRNA has low basal translational efficiency in proximal tubule cells; however, its translation is stimulated by profibrotic cytokines. We studied the role of the multifunctional Y-box protein-1 (YB-1) in regulating proximal tubule cell TGF-beta1 translation. Using RNA-electrophoretic mobility shift assays and ultraviolet crosslinking, we found two protein complexes of 50 and 100 kDa, which bound to the TGF-beta1 mRNA 5'-untranslated region. Supershift studies using antibodies to YB-1 showed that both sites contained YB-1 as did studies with recombinant YB-1, which demonstrated that it was sufficient to form both complexes. RNA competition experiments confirmed YB-1 binding to the two predicted binding sites; one with high affinity and the other with lower affinity. Strong basal YB-1 association with TGF-beta1 mRNA was found in proximal tubule cells, which decreased when platelet-derived growth factor was used to activate TGF-beta1 translation. In contrast, knockdown of proximal tubule cell YB-1 expression abrogated TGF-beta1 synthesis. Our results suggest that TGF-beta1 translation in proximal tubule cells requires YB-1 binding to a high-affinity site in the 5'-untranslated region of its mRNA; however, binding to a low-affinity site inhibits basal translation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 5' Untranslated Regions / metabolism
  • Cell Line
  • Humans
  • Kidney Tubules, Proximal / metabolism*
  • Protein Biosynthesis* / genetics
  • RNA, Messenger / metabolism
  • RNA-Binding Proteins / metabolism*
  • Transforming Growth Factor beta1 / genetics
  • Transforming Growth Factor beta1 / metabolism*
  • Y-Box-Binding Protein 1 / antagonists & inhibitors
  • Y-Box-Binding Protein 1 / metabolism*


  • 5' Untranslated Regions
  • RNA, Messenger
  • RNA-Binding Proteins
  • Transforming Growth Factor beta1
  • Y-Box-Binding Protein 1