The ciliary protein cystin forms a regulatory complex with necdin to modulate Myc expression.

Abstract

Cystin is a novel cilia-associated protein that is disrupted in the cpk mouse, a well-characterized mouse model of autosomal recessive polycystic kidney disease (ARPKD). Interestingly, overexpression of the Myc gene is evident in animal models of ARPKD and is thought to contribute to the renal cystic phenotype. Using a yeast two-hybrid approach, the growth suppressor protein necdin, known to modulate Myc expression, was found as an interacting partner of cystin. Deletion mapping demonstrated that the C-terminus of cystin and both termini of necdin are required for their mutual interaction. Speculating that these two proteins may function to regulate gene expression, we developed a luciferase reporter assay and observed that necdin strongly activated the Myc P1 promoter, and cystin did so more modestly. Interestingly, the necdin effect was significantly abrogated when cystin was co-transfected. Chromatin immunoprecipitation and electrophoretic mobility shift assays revealed a physical interaction with both necdin and cystin and the Myc P1 promoter, as well as between these proteins. The data suggest that these proteins likely function in a regulatory complex. Thus, we speculate that Myc overexpression in the cpk kidney results from the dysregulation of the cystin-necdin regulatory complex and c-Myc, in turn, contributes to cystogenesis in the cpk mouse.

• Authors: Maoqing Wu, Chaozhe Yang, Binli Tao, Su Bu, Lisa M Guay-Woodford
• Journal: PloS one (PLoS One) Vol. 8 Issue 12 Pg. e83062 ( 2013) ISSN: 1932-6203 [Electronic] United States
• PMID: 24349431 (Publication Type: Journal Article, Research Support, N.I.H., Extramural)

Chemical References

• Cys1 protein, mouse
• Membrane Proteins
• Multiprotein Complexes
• Myc protein, mouse
• Nerve Tissue Proteins
• Nuclear Proteins
• Proto-Oncogene Proteins c-myc
• necdin

Topics

• Animals
• Gene Expression Regulation
• Membrane Proteins (genetics, metabolism)
• Mice
• Multiprotein Complexes (genetics, metabolism)
• Nerve Tissue Proteins (genetics, metabolism)
• Nuclear Proteins (genetics, metabolism)
• Polycystic Kidney, Autosomal Recessive (genetics, metabolism, pathology)
• Promoter Regions, Genetic
• Proto-Oncogene Proteins c-myc (biosynthesis, genetics)