ABCMdb

PMID: 10666020

Rubenstein RC, Zeitlin PL
Sodium 4-phenylbutyrate downregulates Hsc70: implications for intracellular trafficking of DeltaF508-CFTR.
Am J Physiol Cell Physiol. 2000 Feb;278(2):C259-67., [PubMed]

Sentences

No. Mutations Sentence Comment

13 ABCC7 p.Trp1282* IB3-1 cells (genotype ⌬F508/W1282X) that were treated with 0.05-5 mM 4PBA for 2 days in culture demonstrated a dose-dependent reduction in Hsc70 protein immunoreactivity and mRNAlevels. Login to comment 95 ABCC7 p.Trp1282* ABCC7 p.Trp1282* IB3-1 has the CFTR genotype ⌬F508/W1282X and is a model system for study of the intracellular trafficking of ⌬F508-CFTR because the W1282X allele gives rise to an unstable and therefore untranslated mRNA. Login to comment 167 ABCC7 p.Trp1282* G418 promotes read through and stabilization of the otherwise unstable mRNA derived from the W1282X missense allele present in IB3-1 cells and results in the appearance of CFTR channel activity at the IB3-1 plasma membrane (2). Login to comment 185 ABCC7 p.Trp1282* G418, which acts on the W1282X allele and not ⌬F508-CFTR, had little effect on Hsc70 or Hsp90 but increased Hsp40 and Hsp70 immunoreactivity. Login to comment 186 ABCC7 p.Trp1282* ABCC7 p.Trp1282* Although it seems logical that increased Hsc70 might lead to reduced trafficking of CFTR derived from the W1282X allele, the W1282X-derived CFTR would have wild-type structure in the region of F508, and the F508 region may be a critical determinant of CFTR affinity for Hsc70. Login to comment 209 ABCC7 p.Trp1282* This is also consistent with G418 acting on the W1282X-CFTR allele present in IB3-1 and not on the ⌬F508 allele that is the target of 4PBA, glycerol, or butyrate. Login to comment