ABCMdb

PMID: 16977321

Carlson EJ, Pitonzo D, Skach WR
p97 functions as an auxiliary factor to facilitate TM domain extraction during CFTR ER-associated degradation.
EMBO J. 2006 Oct 4;25(19):4557-66. Epub 2006 Sep 14., 2006-10-04 [PubMed]

Sentences

No. Mutations Sentence Comment

133 ABCC7 p.Lys95Ala ABCC7 p.Glu92Ala The TM1-2 E92A/K95A mutations had a striking effect, decreasing the initial degradation rate by B2.5-fold (0.2870.03/min) in the presence of p97 (Figure 6E and F), and further decreasing the degradation rate by an additional 2.3-fold following p97 depletion (0.1270.01/min). Login to comment 160 ABCC7 p.Lys95Ala ABCC7 p.Glu92Ala (B) Carbonate extraction of wild-type and E92A/K95A polypeptides. Login to comment 179 ABCC7 p.Lys95Ala ABCC7 p.Glu92Ala This also held true in the absence of p97 where the degradation rate of isolated NBD1 and NBD1-R domains was significantly faster than TMD1 and TM12(E92A/K95A). Login to comment 205 ABCC7 p.Lys95Ala ABCC7 p.Glu92Ala deg. rate -p97 (%/min) %increasewithp97 CFTR TMD1 TM1-2wt NBD-R NBD140 80 120 0 160 TM1-2 (E92A/K95A ) Figure 8 P97 effect is inversely related to the rate of degradation. Login to comment 221 ABCC7 p.Lys95Ala ABCC7 p.Glu92Ala Thus, p97 may play a key role in stimulating TM1-2 E92A/K95A degradation by providing a second step for substrate partitioning, thereby generating a locally unfolded domain that preferentially engages the AAA-ATPase ring of the 19S RC. Login to comment 237 ABCC7 p.Lys95Ala ABCC7 p.Glu92Ala Before pelleting, TM1-2 E92A/K95A was released from ribosomes by addition of 1 mM puromycin. Login to comment