FRINK Linked Data Fragments server

Matches in SemOpenAlex for { <https://semopenalex.org/work/W4283324710> ?p ?o ?g. }

• W4283324710 endingPage "6947" @default.
• W4283324710 startingPage "6947" @default.
• W4283324710 abstract "Phospholamban (PLN), a key modulator of Ca2+-homeostasis, inhibits sarcoplasmic reticulum (SR) calcium-ATPase (SERCA2a) and regulates cardiac contractility. The human PLN mutation R14del has been identified in arrhythmogenic cardiomyopathy patients worldwide and is currently extensively investigated. In search of the molecular mechanisms mediating the pathological phenotype, we examined PLN-R14del associations to known PLN-interacting partners. We determined that PLN-R14del interactions to key Ca2+-handling proteins SERCA2a and HS-1-associated protein X-1 (HAX-1) were enhanced, indicating the super-inhibition of SERCA2a's Ca2+-affinity. Additionally, histidine-rich calcium binding protein (HRC) binding to SERCA2a was increased, suggesting the inhibition of SERCA2a maximal velocity. As phosphorylation relieves the inhibitory effect of PLN on SERCA2a activity, we examined the impact of phosphorylation on the PLN-R14del/SERCA2a interaction. Contrary to PLN-WT, phosphorylation did not affect PLN-R14del binding to SERCA2a, due to a lack of Ser-16 phosphorylation in PLN-R14del. No changes were observed in the subcellular distribution of PLN-R14del or its co-localization to SERCA2a. However, in silico predictions suggest structural perturbations in PLN-R14del that could impact its binding and function. Our findings reveal for the first time that by increased binding to SERCA2a and HAX-1, PLN-R14del acts as an enhanced inhibitor of SERCA2a, causing a cascade of molecular events contributing to impaired Ca2+-homeostasis and arrhythmogenesis. Relieving SERCA2a super-inhibition could offer a promising therapeutic approach for PLN-R14del patients." @default.
• W4283324710 created "2022-06-24" @default.
• W4283324710 creator A5007178671 @default.
• W4283324710 creator A5039759348 @default.
• W4283324710 creator A5059841903 @default.
• W4283324710 creator A5068792421 @default.
• W4283324710 creator A5080329479 @default.
• W4283324710 date "2022-06-22" @default.
• W4283324710 modified "2023-09-26" @default.
• W4283324710 title "Aberrant PLN-R14del Protein Interactions Intensify SERCA2a Inhibition, Driving Impaired Ca2+ Handling and Arrhythmogenesis" @default.
• W4283324710 cites W1539099740 @default.
• W4283324710 cites W1803102843 @default.
• W4283324710 cites W1970953058 @default.
• W4283324710 cites W1971048452 @default.
• W4283324710 cites W1975322691 @default.
• W4283324710 cites W2010576268 @default.
• W4283324710 cites W2010638459 @default.
• W4283324710 cites W2018019689 @default.
• W4283324710 cites W2030603906 @default.
• W4283324710 cites W2033608440 @default.
• W4283324710 cites W2039935249 @default.
• W4283324710 cites W2043274355 @default.
• W4283324710 cites W2044227913 @default.
• W4283324710 cites W2057377709 @default.
• W4283324710 cites W2060075866 @default.
• W4283324710 cites W2063779850 @default.
• W4283324710 cites W2068250491 @default.
• W4283324710 cites W2069083263 @default.
• W4283324710 cites W2075245425 @default.
• W4283324710 cites W2080625632 @default.
• W4283324710 cites W2099540110 @default.
• W4283324710 cites W2105195825 @default.
• W4283324710 cites W2120222096 @default.
• W4283324710 cites W2123695271 @default.
• W4283324710 cites W2139331439 @default.
• W4283324710 cites W2139595741 @default.
• W4283324710 cites W2145580878 @default.
• W4283324710 cites W2146665756 @default.
• W4283324710 cites W2158714558 @default.
• W4283324710 cites W2166132258 @default.
• W4283324710 cites W2170124209 @default.
• W4283324710 cites W2171068341 @default.
• W4283324710 cites W2293658565 @default.
• W4283324710 cites W2742856042 @default.
• W4283324710 cites W2770000996 @default.
• W4283324710 cites W2792980560 @default.
• W4283324710 cites W2904739952 @default.
• W4283324710 cites W2904931379 @default.
• W4283324710 cites W2915941065 @default.
• W4283324710 cites W2916393318 @default.
• W4283324710 cites W2972604037 @default.
• W4283324710 cites W3036745709 @default.
• W4283324710 cites W3081749934 @default.
• W4283324710 cites W3082672803 @default.
• W4283324710 cites W3089368055 @default.
• W4283324710 cites W3089377634 @default.
• W4283324710 cites W3113156707 @default.
• W4283324710 cites W3159185597 @default.
• W4283324710 cites W3160578854 @default.
• W4283324710 cites W3165350640 @default.
• W4283324710 cites W3166496080 @default.
• W4283324710 cites W4200136330 @default.
• W4283324710 cites W4200302694 @default.
• W4283324710 cites W4200589388 @default.
• W4283324710 cites W4206918415 @default.
• W4283324710 cites W4212918097 @default.
• W4283324710 cites W4213148808 @default.
• W4283324710 doi "https://doi.org/10.3390/ijms23136947" @default.
• W4283324710 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/35805951" @default.
• W4283324710 hasPublicationYear "2022" @default.
• W4283324710 type Work @default.
• W4283324710 citedByCount "7" @default.
• W4283324710 countsByYear W42833247102022 @default.
• W4283324710 countsByYear W42833247102023 @default.
• W4283324710 crossrefType "journal-article" @default.
• W4283324710 hasAuthorship W4283324710A5007178671 @default.
• W4283324710 hasAuthorship W4283324710A5039759348 @default.
• W4283324710 hasAuthorship W4283324710A5059841903 @default.
• W4283324710 hasAuthorship W4283324710A5068792421 @default.
• W4283324710 hasAuthorship W4283324710A5080329479 @default.
• W4283324710 hasBestOaLocation W42833247101 @default.
• W4283324710 hasConcept C11960822 @default.
• W4283324710 hasConcept C134018914 @default.
• W4283324710 hasConcept C158617107 @default.
• W4283324710 hasConcept C17137333 @default.
• W4283324710 hasConcept C181199279 @default.
• W4283324710 hasConcept C185592680 @default.
• W4283324710 hasConcept C23265538 @default.
• W4283324710 hasConcept C2781414619 @default.
• W4283324710 hasConcept C39133596 @default.
• W4283324710 hasConcept C55493867 @default.
• W4283324710 hasConcept C63645605 @default.
• W4283324710 hasConcept C86803240 @default.
• W4283324710 hasConcept C95444343 @default.
• W4283324710 hasConceptScore W4283324710C11960822 @default.
• W4283324710 hasConceptScore W4283324710C134018914 @default.
• W4283324710 hasConceptScore W4283324710C158617107 @default.
• W4283324710 hasConceptScore W4283324710C17137333 @default.

• next