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lördag 9 november 2024

PDIA6 ja insuliini / mutatoitunut insuliini. UPR koneiston säätymisistä.

 

2 results

Conserved C272/278 in b domain regulate the function of PDI-P5 to make lysozymes trypsin-resistant forms via significant intermolecular disulfide cross-linking.
Miyakawa M, Zukeran G, Wada Y, Akama K. Biochim Biophys Acta. 2015 May;1854(5):485-91. doi: 10.1016/j.bbapap.2015.02.014. Epub 2015 Feb 27. PMID: 25731082
Protein disulfide isomerase-P5 (P5) is thought to have important functions as an oxidoreductase, however, molecular functions of P5 have not been fully elucidated. We have reported that P5 has insulin reductase activity and inhibits lysozyme refolding by formation of lysoz … 
 

 
Thioredoxin-interacting protein regulates protein disulfide isomerases and endoplasmic reticulum stress.
Lee S, Min Kim S, Dotimas J, Li L, Feener EP, Baldus S, Myers RB, Chutkow WA, Patwari P, Yoshioka J, Lee RT. EMBO Mol Med. 2014 Jun;6(6):732-43. doi: 10.15252/emmm.201302561. Epub 2014 Apr 6. PMID: 24843047 Free PMC article.
Accumulation of unfolded or misfolded proteins represents the condition of ER stress and triggers the unfolded protein response (UPR), a key mechanism linking supply of excess nutrients to insulin resistance and type 2 diabetes in obesity. The ER harbors proteins th … 
 
 


Protein Disulfide Isomerase A6 Controls the Decay of IRE1α Signaling via Disulfide-Dependent Association

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  Our data thus suggest that PDIA6 ablation does not significantly induce IRE1 activation nor does it affect the onset of IRE1 signaling. Rather, it affects the inactivation of IRE1, as measured by attenuation of phosphorylation of the sensor, XBP1 splicing, and JNK activation, in response to both chemical stress and misfolded proteins.
 
 All together, we conclude that PDIA6 affects UPR signaling via the IRE1 and PERK sensors, but not via ATF6. Because PERK and IRE1 do not heterodimerize and expression or activation of PERK does not impact the ribonuclease activity of IRE1 (Lin et al., 2009), the data suggest that PDIA6 impacts each sensor independently.

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