.png){kind=icon}
Return
HAP40 protein levels are huntingtin-dependent and decrease in Huntington disease
.png){kind=icon}
OA
AI
DOI：10.1016/j.nbd.2021.105476.png)
.png){kind=icon}
.png){kind=icon}
Share.png){kind=icon}
Save
Abstract
En 中文
The huntingtin-associated protein 40 (HAP40) is an abundant interactor of huntingtin (HTT). In complexes of these proteins, HAP40 tightly binds to HTT in a cleft formed by two larger domains rich in HEAT repeats, and a smaller bridge domain connecting the two. We show that HAP40 steady-state protein levels are directly dependent on HTT (both normal and mutant HTT) and that HAP40 is strongly stabilized by the interaction with HTT resulting in an at least 5-fold increase in HAP40's half-life when bound to HTT. Cellular HAP40 protein levels were reduced in primary fibroblasts and lymphoblasts of Huntington Disease (HD) patients and in brain tissue of a full-length HTT mouse model of HD, concomitant with decreased soluble HTT levels in these cell types. This data and our previous demonstration of coevolution between HTT and HAP40 and evolutionary conservation of their interaction suggest that HAP40 is an obligate interaction partner of HTT. Our observation of reduced HAP40 levels in HD invites further studies, whether HAP40 loss-of-function contributes to the pathophysiology of HD.
Keywords:
HAP40
Huntingtin
Huntington disease
Protein stability
Obligate partner
AI Summary
Key information extracted from the uploaded paper, including a brief overview, abstract, background, key highlights, visual analysis, and future outlook.
Journal
IF:
5.6
Papers:
6.9K
Citations:
2.1W
Organization
Cited Papers
A Coordinated Interdependent Protein Circuitry Stabilizes the Kinetochore Ensemble to Protect CENP-A in the Human Pathogenic Yeast Candida albicans.png)
PLOS GENETICSOAAI
PLOS GENETICSIF3.7
OAAIShareSaveShareSaveShareSaveFast degradation of the auxiliary subunit of Na+/K+-ATPase in the plasma membrane of HeLa cells
PREAI
ShareSaveThe ssDNA-binding protein MEIOB acts as a dosage-sensitive regulator of meiotic recombinationNUCLEIC ACIDS RESEARCHOAAI
NUCLEIC ACIDS RESEARCHIF13.1
OAAIShareSave
View more