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Publication : Polycystin-1 and polycystin-2 regulate the cell cycle through the helix-loop-helix inhibitor Id2.

First Author  Li X Year  2005
Journal  Nat Cell Biol Volume  7
Issue  12 Pages  1202-12
PubMed ID  16311606 Mgi Jnum  J:182496
Mgi Id  MGI:5315699 Doi  10.1038/ncb1326
Citation  Li X, et al. (2005) Polycystin-1 and polycystin-2 regulate the cell cycle through the helix-loop-helix inhibitor Id2. Nat Cell Biol 7(12):1202-12
abstractText  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.
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