Siah-1 interacts with the intracellular region of polycystin-1 and affects its stability via the ubiquitin-proteasome pathway

Hyunho Kim, Woocho Jeong, Kwangseog Ahn, Curie Ahn, Seong Man Kang

Research output: Contribution to journalArticle

26 Citations (Scopus)

Abstract

Autosomal dominant polycystic kidney disease, characterized by extensive formation of renal cysts and progressive renal failure, is a genetic disorder caused by mutations in the MD1 and PKD2 genes. The PKD1 gene product, polycystin-1, is a transmembrane protein with its N-terminus facing the extracellular region and C-terminus facing the cytoplasm. Polycystin-1 seems to be involved in regulating cell growth and maturation, but the precise mechanisms are not yet well defined. For investigating the function of the intracellular region of polycystin-1, the C-terminal cytoplasmic fragment of polycystin- 1, PKD1-C, was used as bait in two-hybrid screening, and a polycystin-1-binding protein, the human homologue of Drosophila Seven in Absentia (Siah-1), which has a RING domain and promotes the ubiquitin-dependent proteasome pathway, was identified. It was shown that PKD1-C interacts with Siah-1 in vivo. In addition, interaction with Siah-1 induces the degradation of PKD1-C, shortening its half-life. PKD1-C and CD4 chimeric proteins, which are attached to the plasma membrane, also show similar results. Furthermore, ubiquitination and degradation of PKD1-C are increased in the presence of Siah-1, and overexpression of Siah-1 protein promotes the degradation of polycystin-1 via the ubiquitin-proteasome pathway. These results suggest that polycystin-1 is regulated by Siah-1 through the ubiquitin-dependent proteasome pathway.

Original languageEnglish
Pages (from-to)2042-2049
Number of pages8
JournalJournal of the American Society of Nephrology
Volume15
Issue number8
DOIs
Publication statusPublished - 2004 Aug 1

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Proteasome Endopeptidase Complex
Ubiquitin
Autosomal Dominant Polycystic Kidney
Inborn Genetic Diseases
Ubiquitination
polycystic kidney disease 1 protein
Proteolysis
Genes
Drosophila
Renal Insufficiency
Half-Life
Cysts
Carrier Proteins
Cytoplasm
Proteins
Cell Membrane
Kidney
Mutation
Growth

ASJC Scopus subject areas

  • Nephrology

Cite this

Siah-1 interacts with the intracellular region of polycystin-1 and affects its stability via the ubiquitin-proteasome pathway. / Kim, Hyunho; Jeong, Woocho; Ahn, Kwangseog; Ahn, Curie; Kang, Seong Man.

In: Journal of the American Society of Nephrology, Vol. 15, No. 8, 01.08.2004, p. 2042-2049.

Research output: Contribution to journalArticle

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