Deep mutational scanning reveals a correlation between degradation and toxicity of thousands of aspartoacylase variants

Autor: Martin Grønbæk-Thygesen, Vasileios Voutsinos, Kristoffer E. Johansson, Thea K. Schulze, Matteo Cagiada, Line Pedersen, Lene Clausen, Snehal Nariya, Rachel L. Powell, Amelie Stein, Douglas M. Fowler, Kresten Lindorff-Larsen, Rasmus Hartmann-Petersen

Publikováno v: Nature Communications, Vol 15, Iss 1, Pp 1-18 (2024)

Abstract Unstable proteins are prone to form non-native interactions with other proteins and thereby may become toxic. To mitigate this, destabilized proteins are targeted by the protein quality control network. Here we present systematic studies of

Externí odkaz: https://doaj.org/article/78779a3126b8415c806c43decd7c4a0b

Mapping the degradation pathway of a disease-linked aspartoacylase variant.

Autor: Sarah K Gersing, Yong Wang, Martin Grønbæk-Thygesen, Caroline Kampmeyer, Lene Clausen, Martin Willemoës, Claes Andréasson, Amelie Stein, Kresten Lindorff-Larsen, Rasmus Hartmann-Petersen

Publikováno v: PLoS Genetics, Vol 17, Iss 4, p e1009539 (2021)

Canavan disease is a severe progressive neurodegenerative disorder that is characterized by swelling and spongy degeneration of brain white matter. The disease is genetically linked to polymorphisms in the aspartoacylase (ASPA) gene, including the su

Externí odkaz: https://doaj.org/article/5a6704a5a3084b048fd91b196f25c0dc

Evolutionarily conserved chaperone-mediated proteasomal degradation of a disease-linked aspartoacylase variant

Autor: Kresten Lindorff-Larsen, Rasmus Hartmann-Petersen, Claes Andréasson, Caroline Kampmeyer, Amelie Stein, Martin Grønbæk-Thygesen, Yong Wang, Sarah K. Gersing, Lene Clausen

Canavan disease is a severe progressive neurodegenerative disorder that is characterized by swelling and spongy degeneration of brain white matter. The disease is genetically linked to polymorphisms in the aspartoacylase (ASPA) gene, including the su

Externí odkaz: https://explore.openaire.eu/search/publication?articleId=doi_________::ce3df7e02c64d82c224ed75fab58f0e3
https://doi.org/10.1101/2020.09.04.283028

Folliculin variants linked to Birt-Hogg-Dubé syndrome are targeted for proteasomal degradation

Autor: Kresten Lindorff-Larsen, Lene Clausen, Rasmus Hartmann-Petersen, Cecilie L. Søltoft, Michael Lisby, Sofie V. Nielsen, Amelie Stein, Tommer Ravid, Martin Grønbæk-Thygesen, Lasse Nygaard

Publikováno v: PLoS Genetics, Vol 16, Iss 11, p e1009187 (2020)
Clausen, L, Stein, A, Grønbæk-Thygesen, M, Nygaard, L, Søltoft, C L, Nielsen, S V, Lisby, M, Ravid, T, Lindorff-Larsen, K & Hartmann-Petersen, R 2020, ' Folliculin variants linked to Birt-Hogg-Dubé syndrome are targeted for proteasomal degradation ', PLOS Genetics, vol. 16, no. 11, e1009187 . https://doi.org/10.1371/journal.pgen.1009187
PLoS Genetics

Germline mutations in the folliculin (FLCN) tumor suppressor gene are linked to Birt-Hogg-Dubé (BHD) syndrome, a dominantly inherited genetic disease characterized by predisposition to fibrofolliculomas, lung cysts, and renal cancer. Most BHD-linked

Externí odkaz: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::7f7054624c66ff607e8a75f717c39280
https://doi.org/10.1371/journal.pgen.1009187

Protein stability and degradation in health and disease

Autor: Amelie Stein, Rasmus Hartmann-Petersen, Amanda B Abildgaard, Lene Clausen, Sarah K. Gersing, Kresten Lindorff-Larsen

The cellular proteome performs highly varied functions to sustain life. Since most of these functions require proteins to fold properly, they can be impaired by mutations that affect protein structure, leading to diseases such as Alzheimer's disease,

Externí odkaz: https://explore.openaire.eu/search/publication?articleId=doi_________::2316b273db1ccdd609c11c789b31fce7
https://doi.org/10.1016/bs.apcsb.2018.09.002