ABCMdb

ABCC7 p.Lys1080Arg

None has been submitted yet.

Publications

PMID: 24777605 [PubMed] Lee S et al: "Interference with ubiquitination in CFTR modifies stability of core glycosylated and cell surface pools."

No. Sentence Comment

73 We hypothe- TABLE 1 Primers for site-directed mutagenesis Mutation Directiona Sequence (5=-3=)b K14R F GGCCAGCGTTGTCTCCAGACTTTTTTTCAGCTGGACC R GGTCCAGCTGAAAAAAAGTCTGGAGACAACGCTGGCC K68R F GGCTTCAAAGAAAAATCCTAGACTCATTAATGCCCTTCGGCG R CGCCGAAGGGCATTAATGAGTCTAGGATTTTTCTTTGAAGCC K710R F CCAATCAACTCTATACGAAGATTTTCCATTGTGCAAAAG R CTTTTGCACAATGGAAAATCTTCGTATAGAGTTGATTGG K716R F GAAAATTTTCCATTGTGCAAAGGACTCCCTTACAAATGAATGG R CCATTCATTTGTAAGGGAGTCCTTTGCACAATGGAAAATTTTC K710/716R F CCAATCAACTCTATACGAAGATTTTCCATTGTGCAAAGGACTCCCTTACAAATGAATGG R CCATTCATTTGTAAGGGAGTCCTTTGCACAATGGAAAATCTTCGTATAGAGTTGATTGG K1041R F CCTCACAGCAATTCAGACAACTGGAATCTGAAG R CTTCAGATTCCAGTTGTCTGAGTTGCTGTGAGG K1080R F GAAACTCTGTTCCACAGAGCTCTGAATTTACATAC R GTATGTAAATTCAGAGCTCTGTGGAACAGAGTTTC K1218R F GATCTCACAGCAAGATACACAGAAGG R CCTTCTGTGTATCTTGCTGTGAGATC a F, forward; R, reverse. Login to comment
86 We generated K1041R and K1080R mutants and expressed them in IB3-1. Login to comment
104 The observed reduction in expression of K710R, K716R, K710/ 716R, K1041R, and K1080R CFTRs might be the consequence of disordered conformational structure or folding/assembly. Login to comment
130 This immunoblot demonstrates increased levels of band C CFTR expression from the K14R, K68R, and K1218R cDNA vectors and decreased levels of band C CFTR expression in K710R, K716R, K710/716R, and K1080R vectors. Login to comment
157 K1080R and K1218R mutants displayed both bands B and C after proteasomal inhibition. Login to comment
158 This supports the hypothesis that the K1080R and K1218R mutants undergo the same degree of proteasomal degradation as wild-type CFTR and are still trafficked. Login to comment
159 Prevention of proteolysis at the lysosome accumulates more C band K1041R and K1080R. Login to comment
169 (C) The results from expression of control vector, wt CFTR, K1041R, K1080R, and K1218R with and without proteasomal or lysosomal inhibition are shown in representative blots similar to the results show in panel A. MG132 rescues band B from K1041R to some extent, as well as a small portion of band C. Login to comment
170 Lysosomal inhibition recovers some band C. K1080R is rescued by both MG132 and lysosome inhibition. Login to comment
174 pression of K1080R C band and improved the K1218R mutant, indicating that the K1218R mutant can avoid lysosomal degradation. Login to comment
175 Therefore, these data suggest that K1041R and K1080R mutants are degraded at the proteasome and lysosome, respectively. Login to comment
194 K14R, K1080R, and K1218R but not K1041R reach the cell surface. Login to comment
200 There were decreased levels of cell surface CFTR detection in the K68R, K710R, K716R, K710/ K716R, and K1041R mutant forms of CFTR, but the wild-type, K14R, K1080R, and K1218R mutants accumulated similar levels of visible cell surface CFTR. Login to comment
201 Analysis of the Z stack of images for the wild type, K68R, K710R, K1080R, and K1218R confirmed that the CFTR immunostaining, shown in red, resided at the apical surface in these nonpermeabilized cells (data not shown). Login to comment
207 Again, there was a reduction in immunodetectable CFTR (K14R, K68R, K710R, K716R, K710/716R, and K1080R forms) in cell surface membranes compared to wild-type levels. Login to comment
214 Preventing ubiquitination at K14R, K1080R, and K1218R allows the mutant protein to gain access to the cell surface. Login to comment
218 Control vector, wt CFTR, K14R, K68R, K710R, K716R, K710/716R, K1041R, K1080R, and K1218R were expressed in IB3-1 cells for 48 h. CFTR was immunoprecipitated (IP) with M3A7 as described in Materials and Methods and separated by SDS-PAGE. Login to comment
222 K-63-linked ubiquitin appears to be increased in the K1080R mutant. Login to comment
226 FIG 6 K-to-R mutation alters the stability of CFTR protein, and wt CFTR, K14R, K1080R, and K1218R, but not K1041R, are detectable at the cell surface. Login to comment
241 HDAC6 was abundant in all cases, and ZO-1 was conspicuously absent from the K1080R and K1218R mutants. Login to comment
252 The F508del from the surface of cells expressing wt CFTR, K14R, K1080R, and K1218R. Login to comment
261 Band C was most reduced in K1041R and highest in the wt, K1080R, and K1218R, consistent with data in panels A and B. Login to comment
274 We did not detect ZO-1 in the K1080R or K1218R complex. Login to comment
275 Since ZO-1 interacts with PDZ domains, the reduced interactions in K14R, K68R, K710R, K716R, K710/716R, and K1041R and the absence of interactions with K1080R and K1218R raise the issue of alternative trafficking routes that are not dependent on the C-tail PDZ domain. Login to comment
278 Poly- or monoubiquitination in K14, K68, K710, K716, 1041, K1080, and K1218 sites allows CFTR to pass through its regular quality control process, producing adequate band C. K710R, K716R, K710/K716R, and K1080R mutants undergo some proteasome- and some lysosome-dependent degradation, whereas K1041R is primarily degraded by the proteasome. Login to comment
296 Interestingly, ZO-1 was highly abundant in complexes formed with wt CFTR; K14R, K68R, K710R, K716R, K710/716R, and K1041R mutants bound less ZO-1, whereas K1080R and K1218R mutant complexes had none. Login to comment
297 This result indicates that interrupting ubiquitination of CFTR in lysine residue 1218 weakens its interaction with ZO-1 complex and that this decreased affinity to PDZ binding proteins might decelerate the degradative pathway, whereas reduced interaction with ZO-1 in the K1080R mutant accelerated degradation. Login to comment
300 Table 3 lists the findings: K14X (stop), K68E, K68N, K710X (stop), K1080Q, K1080R, and K1080I mutations already exist in human genes. Login to comment
302 The missense mutants may resemble ours, such as the K1080R mutant. Login to comment
303 It is also interesting that the K1080R mutant is capable of C band expression. Login to comment