The Birt-Hogg-Dubé tumor suppressor folliculin negatively regulates ribosomal RNA synthesis

Kriti Gaur, Jinghong Li, Dakun Wang, Pranabananda Dutta, Shian Jang Yan, Amy Tsurumi, Hartmut Land, Guan Wu, Willis X. Li

Research output: Contribution to journalArticlepeer-review

15 Citations (Scopus)


Birt-Hogg-Dubé syndrome (BHD) is a human cancer disorder caused by mutations in the tumor suppressor gene Folliculin (FLCN) with unknown biological functions. Here, we show that the Drosophila homolog of FLCN, dFLCN (a.k.a. dBHD) localizes to the nucleolus and physically interacts with the 19S proteasomal ATPase, Rpt4, a nucleolar resident and known regulator of rRNA transcription. Downregulation of dFLCN resulted in an increase in nucleolar volume and upregulation of rRNA synthesis, whereas dFLCN overexpression reduced rRNA transcription and counteracted the effects of Rpt4 on rRNA production by preventing the association of Rpt4 with the rDNA locus. We further show that human FLCN exhibited evolutionarily conserved function and that Rpt4 knockdown inhibits the growth of FLCN-deficient human renal cancer cells in mouse xenografts. Our study suggests that FLCN functions as a tumor suppressor by negatively regulating rRNA synthesis.

Original languageEnglish
Article numberdds428
Pages (from-to)284-299
Number of pages16
JournalHuman Molecular Genetics
Issue number2
Publication statusPublished - 2013 Jan

All Science Journal Classification (ASJC) codes

  • Molecular Biology
  • Genetics
  • Genetics(clinical)


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