title: Polycystin-1C terminus cleavage and its relation with polycystin-2, two proteins involved in polycystic kidney disease.
abstract: Autosomal dominant polycystic kidney disease (ADPKD), a most common genetic cause of chronic renal failure, is characterized by the progressive development and enlargement of cysts in kidneys and other organs. The cystogenic process is highly complex and involves a high proliferative rate, increased apoptosis, altered protein sorting, changed secretory characteristics, and disorganization of the extracellular matrix. ADPKD is caused by mutations in the genes encoding polycystin-1 (PC-1) or polycystin-2 (PC-2). PC-1 undergoes multiple cleavages that intervene in several signaling pathways involved in cellular proliferation and differentiation mechanisms. One of these cleavages releases the cytoplasmic C-terminal tail of PC-1. In addition, the C-terminal cytoplasmic tails of PC-1 and PC-2 interact in vitro and in vivo. The purpose of this review is to summarize recent literature that suggests that PC-1 and PC-2 may function through a common signaling pathway necessary for normal tubulogenesis. We hope that a better understanding of PC-1 and PC-2 protein function will lead to progress in diagnosis and treatment for ADPKD.
authors.affiliation: Department of Cell Biology and Physiology, University of Pittsburgh, Pittsburgh, PA, USA. cab199@pitt.edu
authors.forename: Claudia A
authors.initials: CA
authors.lastname: Bertuccio
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Caplan
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000502:physiology; D015220:Calcium Channels / Q000378:metabolism; D002467:Cell Nucleus / Q000378:metabolism; D049109:Cell Proliferation; D000242:Cyclic AMP / Q000378:metabolism; D006801:Humans; D007684:Kidney Tubules / Q000378:metabolism; D009154:Mutation; D016891:Polycystic Kidney, Autosomal Dominant / Q000235:genetics / Q000378:metabolism*; D050396:TRPP Cation Channels / Q000378:metabolism*
chemical_list: D015220:Calcium Channels; D000242:Cyclic AMP; D050396:TRPP Cation Channels
keywords: C-terminal tail (CTT) cleavage of polycystin-1; Ca2+; cAMP; mTOR; polycystin-1 (PC-1); polycystin-2 (PC-2); primary cilium