Nat Cell Biol. 2005 Dec;7(12):1202-12. Epub 2005 Nov 27.
Polycystin-1 and polycystin-2 regulate the cell cycle through the helix-loop-helix inhibitor Id2.
Li, X., Luo, Y., Starremans, P. G., McNamara, C. A., Pei, Y., Zhou, J.,
["Renal Division, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA 02115, USA."]
["Renal Division, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA 02115, USA."]
Autosomal-dominant polycystic kidney disease (ADPKD) is the most common hereditary kidney disease and is characterized by progressive cyst formation and ultimate loss of renal function. Increased cell proliferation is a key feature of the disease. Here, we show that the ADPKD protein polycystin-2 (PC2) regulates the cell cycle through direct interaction with Id2, a member of the helix-loop-helix (HLH) protein family that is known to regulate cell proliferation and differentiation. Id2 expression suppresses the induction of a cyclin-dependent kinase inhibitor, p21, by either polycystin-1 (PC1) or PC2. The PC2-Id2 interaction is regulated by PC1-dependent phosphorylation of PC2. Enhanced Id2 nuclear localization is seen in human and mouse cystic kidneys. Inhibition of Id2 expression by RNA interference corrects the hyperproliferative phenotype of PC1 mutant cells. We propose that Id2 has a crucial role in cell-cycle regulation that is mediated by PC1 and PC2.
PMID: 16311606
 Screening
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Validation: In vivo validation
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| TRP channel | Interactor | Method | Species | Region | Species | Organ/tissue | Sample type | |||
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ID2 | Yeast two-hybrid | Human | 679-968 | Human | Fetal kidney | cDNA library | 16311606 | |
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Screening
Validation: In vitro validation
Validation: In vivo validation
Characterization
Functional consequence
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| Validation: In vitro validation
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| Assay with recombinant proteins | Reference | |||||||||
| TRP channel construct | Interactor construct | |||||||||
| TRP channel | Interactor | Method | Species | Region | Expression system | Species | Region | Expression system | ||
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ID2 | Yeast two-hybrid | Human | 679-968 | Yeast | Human | 1-134 | Yeast | 16311606 |
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click the arrow icon to show interactions only between the corresponding TRP channel and the interactor)
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Screening
Validation: In vitro validation
Validation: In vivo validation
Characterization
Functional consequence
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| Validation: In vivo validation
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| Assay with endogenous proteins | Assay with overexpressed proteins | Reference | ||||||||
| Cell or tissue | Cell or tissue | TRP channel construct | Interactor construct | |||||||
| TRP channel | Interactor | Method | Species | Region | Species | Region | ||||
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ID2 | Co-immunoprecipitation | HEK293T | Human | Full-length | Not used | 16311606 | ||
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ID2 | Co-immunofluorescence staining | HEK293T | Human | Full-length | Not used | 16311606 | ||
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Screening
Validation: In vitro validation
Validation: In vivo validation
Characterization
Functional consequence
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top
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| Characterization
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| Binding region mapping | Stoichiometry | Affinity (Kd) | Reference | |||||||
| TRP channel | Interactor | |||||||||
| TRP channel | Interactor | Method | Species | Region | Species | Region | ||||
| TRPP1 |
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ID2 | Yeast two-hybrid | Human | 679-968 | Human | 30-84 | 16311606 | ||
(:
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:
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