FRINK Linked Data Fragments server

Matches in SemOpenAlex for { <https://semopenalex.org/work/W4285798761> ?p ?o ?g. }

• W4285798761 endingPage "e1010302" @default.
• W4285798761 startingPage "e1010302" @default.
• W4285798761 abstract "Perturbation of huntingtin (HTT)'s physiological function is one postulated pathogenic factor in Huntington's disease (HD). However, little is known how HTT is regulated in vivo. In a proteomic study, we isolated a novel ~40kDa protein as a strong binding partner of Drosophila HTT and demonstrated it was the functional ortholog of HAP40, an HTT associated protein shown recently to modulate HTT's conformation but with unclear physiological and pathologic roles. We showed that in both flies and human cells, HAP40 maintained conserved physical and functional interactions with HTT. Additionally, loss of HAP40 resulted in similar phenotypes as HTT knockout. More strikingly, HAP40 strongly affected HTT's stability, as depletion of HAP40 significantly reduced the levels of endogenous HTT protein while HAP40 overexpression markedly extended its half-life. Conversely, in the absence of HTT, the majority of HAP40 protein were degraded, likely through the proteasome. Further, the affinity between HTT and HAP40 was not significantly affected by polyglutamine expansion in HTT, and contrary to an early report, there were no abnormal accumulations of endogenous HAP40 protein in HD cells from mouse HD models or human patients. Lastly, when tested in Drosophila models of HD, HAP40 partially modulated the neurodegeneration induced by full-length mutant HTT while showed no apparent effect on the toxicity of mutant HTT exon 1 fragment. Together, our study uncovers a conserved mechanism governing the stability and in vivo functions of HTT and demonstrates that HAP40 is a central and positive regulator of endogenous HTT. Further, our results support that mutant HTT is toxic regardless of the presence of its partner HAP40, and implicate HAP40 as a potential modulator of HD pathogenesis through its multiplex effect on HTT's function, stability and the potency of mutant HTT's toxicity." @default.
• W4285798761 created "2022-07-19" @default.
• W4285798761 creator A5002790882 @default.
• W4285798761 creator A5019288987 @default.
• W4285798761 creator A5020569668 @default.
• W4285798761 creator A5021213056 @default.
• W4285798761 creator A5032871695 @default.
• W4285798761 creator A5041625330 @default.
• W4285798761 creator A5042994700 @default.
• W4285798761 creator A5047855118 @default.
• W4285798761 creator A5053911309 @default.
• W4285798761 creator A5058689028 @default.
• W4285798761 creator A5060461250 @default.
• W4285798761 creator A5074942308 @default.
• W4285798761 creator A5077902786 @default.
• W4285798761 creator A5078144814 @default.
• W4285798761 creator A5081202392 @default.
• W4285798761 creator A5081275808 @default.
• W4285798761 creator A5082369729 @default.
• W4285798761 creator A5089380840 @default.
• W4285798761 date "2022-07-19" @default.
• W4285798761 modified "2023-10-06" @default.
• W4285798761 title "HAP40 is a conserved central regulator of Huntingtin and a potential modulator of Huntington’s disease pathogenesis" @default.
• W4285798761 cites W1088597131 @default.
• W4285798761 cites W1565076702 @default.
• W4285798761 cites W1579354139 @default.
• W4285798761 cites W1643390591 @default.
• W4285798761 cites W1975932182 @default.
• W4285798761 cites W1977983193 @default.
• W4285798761 cites W1979400866 @default.
• W4285798761 cites W1981397772 @default.
• W4285798761 cites W1985734261 @default.
• W4285798761 cites W1991174366 @default.
• W4285798761 cites W1991311491 @default.
• W4285798761 cites W1993445706 @default.
• W4285798761 cites W1994528729 @default.
• W4285798761 cites W1996511867 @default.
• W4285798761 cites W1999783230 @default.
• W4285798761 cites W2002644780 @default.
• W4285798761 cites W2005927762 @default.
• W4285798761 cites W2009001912 @default.
• W4285798761 cites W2012442320 @default.
• W4285798761 cites W2015041659 @default.
• W4285798761 cites W2018594297 @default.
• W4285798761 cites W2020117714 @default.
• W4285798761 cites W2025578163 @default.
• W4285798761 cites W2028159081 @default.
• W4285798761 cites W2029003444 @default.
• W4285798761 cites W2030410903 @default.
• W4285798761 cites W2034823585 @default.
• W4285798761 cites W2035595951 @default.
• W4285798761 cites W2042567578 @default.
• W4285798761 cites W2050589769 @default.
• W4285798761 cites W2052102093 @default.
• W4285798761 cites W2052112605 @default.
• W4285798761 cites W2057095204 @default.
• W4285798761 cites W2059577521 @default.
• W4285798761 cites W2064312042 @default.
• W4285798761 cites W2064815984 @default.
• W4285798761 cites W2066610953 @default.
• W4285798761 cites W2068749491 @default.
• W4285798761 cites W2069389331 @default.
• W4285798761 cites W2069686570 @default.
• W4285798761 cites W2073282970 @default.
• W4285798761 cites W2082501455 @default.
• W4285798761 cites W2090018999 @default.
• W4285798761 cites W2104582907 @default.
• W4285798761 cites W2106130419 @default.
• W4285798761 cites W2106200048 @default.
• W4285798761 cites W2110643873 @default.
• W4285798761 cites W2112919697 @default.
• W4285798761 cites W2117827556 @default.
• W4285798761 cites W2121642311 @default.
• W4285798761 cites W2122941722 @default.
• W4285798761 cites W2131426455 @default.
• W4285798761 cites W2132082584 @default.
• W4285798761 cites W2135124405 @default.
• W4285798761 cites W2135783352 @default.
• W4285798761 cites W2136218435 @default.
• W4285798761 cites W2138993899 @default.
• W4285798761 cites W2139564084 @default.
• W4285798761 cites W2142180132 @default.
• W4285798761 cites W2163987346 @default.
• W4285798761 cites W2168506830 @default.
• W4285798761 cites W2168803129 @default.
• W4285798761 cites W2291779372 @default.
• W4285798761 cites W2515623196 @default.
• W4285798761 cites W2603868278 @default.
• W4285798761 cites W2607021366 @default.
• W4285798761 cites W2788389336 @default.
• W4285798761 cites W2919539529 @default.
• W4285798761 cites W3121308082 @default.
• W4285798761 cites W3196273022 @default.
• W4285798761 cites W3212415022 @default.
• W4285798761 cites W4211110682 @default.
• W4285798761 cites W4241316979 @default.
• W4285798761 doi "https://doi.org/10.1371/journal.pgen.1010302" @default.
• W4285798761 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/35853002" @default.

• next