Hum Mol Genet. 2008 Oct 15;17(20):3254-62. doi: 10.1093/hmg/ddn221. Epub 2008 Jul 29.

Polycystin-2 down-regulates cell proliferation via promoting PERK-dependent phosphorylation of eIF2alpha.External 2231691f894ba696de1310221b0a0dbbb31a7251e75115c265587c3d9d5f507c

Liang, G., Yang, J., Wang, Z., Li, Q., Tang, Y., Chen, X. Z.,
["Membrane Protein Research Group, Department of Physiology, Faculty of Medicine and Dentistry, University of Alberta, Edmonton, Alberta, Canada T6G 2H7."]
Autosomal dominant polycystic kidney disease (ADPKD) is characterized by the formation of renal, hepatic and pancreatic cysts and by non-cystic manifestations such as abnormal vasculature and embryo left-right asymmetry development. Polycystin-2 (PC2), in which mutations account for 10-15% of ADPKD, was previously shown to down-regulate cell proliferation, but the underlying mechanism was not elucidated. Here, we demonstrate that PC2, but not pathogenic mutants E837X and R872X, represses cell proliferation through promoting the phosphorylation of eukaryotic translation initiation factor eIF2alpha by pancreatic ER-resident eIF2alpha kinase (PERK). ER stress is known to enhance eIF2alpha phosphorylation through up-regulating PERK kinase activity (assessed by phosphorylated PERK). During ER stress, PC2 knockdown also repressed eIF2alpha phosphorylation but did not alter PERK phosphorylation, indicating that PC2 facilitates the eIF2alpha phosphorylation by PERK. PC2 was found to be in the same complex as PERK and eIF2alpha. Together, we demonstrate that PC2 negatively controls cell growth by promoting PERK-mediated eIF2alpha phosphorylation, presumably through physical interaction, which may underlie a pathogenesis mechanism of ADPKD and indicates that PC2 is an important regulator of the translation machinery.
PMID: 18664456External 2231691f894ba696de1310221b0a0dbbb31a7251e75115c265587c3d9d5f507c
Screening Toggle 893349bafcc528f8346c51dc3420151d67b0126b2c122dd1017121c03fa0f69b
  Experimental screening Non-experimental screening Reference
TRP channel construct Interactor source
TRP channel Interactor Method Species Region Species Organ/tissue Sample type
TRPP1 Link 2bd4d11adb659cddf58197a94e201f0a44c55d8d7cb427c624971b42e122c0a4 eIF2ơ Inference Prediction 18664456
TRPP1 Link 2bd4d11adb659cddf58197a94e201f0a44c55d8d7cb427c624971b42e122c0a4 PERK Inference Prediction 18664456
(Link 2bd4d11adb659cddf58197a94e201f0a44c55d8d7cb427c624971b42e122c0a4: click the arrow icon to show interactions only between the corresponding TRP channel and the interactor)
Validation: In vivo validation Toggle 893349bafcc528f8346c51dc3420151d67b0126b2c122dd1017121c03fa0f69b
  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
TRPP1 Link 2bd4d11adb659cddf58197a94e201f0a44c55d8d7cb427c624971b42e122c0a4 eIF2ơ Co-immunoprecipitation Mouse Inner medullary collecting duct 18664456
TRPP1 Link 2bd4d11adb659cddf58197a94e201f0a44c55d8d7cb427c624971b42e122c0a4 eIF2ơ Co-immunofluorescence staining HEK293T Human Full-length Not used 18664456
TRPP1 Link 2bd4d11adb659cddf58197a94e201f0a44c55d8d7cb427c624971b42e122c0a4 PERK Co-immunoprecipitation Mouse Inner medullary collecting duct 18664456
TRPP1 Link 2bd4d11adb659cddf58197a94e201f0a44c55d8d7cb427c624971b42e122c0a4 PERK Co-immunoprecipitation HEK293T Not used Mouse Full-length 18664456
TRPP1 Link 2bd4d11adb659cddf58197a94e201f0a44c55d8d7cb427c624971b42e122c0a4 PERK Co-immunoprecipitation HEK293T Human Full-length Not used 18664456
(Link 2bd4d11adb659cddf58197a94e201f0a44c55d8d7cb427c624971b42e122c0a4: click the arrow icon to show interactions only between the corresponding TRP channel and the interactor)
TRP / Interactor

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