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 journalArticle

13 Citations (Scopus)

Abstract

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
Volume22
Issue number2
DOIs
Publication statusPublished - 2013 Jan 1

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Ribosomal RNA
Estrone
Neoplasms
Ribosomal DNA
Tumor Suppressor Genes
Renal Cell Carcinoma
Heterografts
Drosophila
Adenosine Triphosphatases
Up-Regulation
Down-Regulation
Mutation
Growth

All Science Journal Classification (ASJC) codes

  • Genetics
  • Genetics(clinical)
  • Molecular Biology

Cite this

Gaur, Kriti ; Li, Jinghong ; Wang, Dakun ; Dutta, Pranabananda ; Yan, Shian-Jang ; Tsurumi, Amy ; Land, Hartmut ; Wu, Guan ; Li, Willis X. / The Birt-Hogg-Dubé tumor suppressor folliculin negatively regulates ribosomal RNA synthesis. In: Human Molecular Genetics. 2013 ; Vol. 22, No. 2. pp. 284-299.
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Gaur, K, Li, J, Wang, D, Dutta, P, Yan, S-J, Tsurumi, A, Land, H, Wu, G & Li, WX 2013, 'The Birt-Hogg-Dubé tumor suppressor folliculin negatively regulates ribosomal RNA synthesis', Human Molecular Genetics, vol. 22, no. 2, dds428, pp. 284-299. https://doi.org/10.1093/hmg/dds428

The Birt-Hogg-Dubé tumor suppressor folliculin negatively regulates ribosomal RNA synthesis. / Gaur, Kriti; Li, Jinghong; Wang, Dakun; Dutta, Pranabananda; Yan, Shian-Jang; Tsurumi, Amy; Land, Hartmut; Wu, Guan; Li, Willis X.

In: Human Molecular Genetics, Vol. 22, No. 2, dds428, 01.01.2013, p. 284-299.

Research output: Contribution to journalArticle

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AU - Gaur, Kriti

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AU - Yan, Shian-Jang

AU - Tsurumi, Amy

AU - Land, Hartmut

AU - Wu, Guan

AU - Li, Willis X.

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