TDP-43 proteinubiquitinationtardbpamyotrophic lateral sclerosisDeposition of intracellular ubiquitin inclusion in motor neurons is one of the leading pathogenic mechanisms of amyotrophic lateral sclerosis (ALS). The transactive response DNA binding protein-43 (TDP-43) is the main component of intracellular ...
9. Pengcheng Ma, Ning-Ning Song, Yongxin Li, et al. (2019). Fine-turning of Shh/Gli signaling gradient by non-proteolytic ubiquitination during neural patterning. Cell Reports 28: 541-553 10. Pengcheng Ma, Xiangcai Yang, Qinghua Kong, et al. (2014). The ubiquitin ligase RNF220 enhances...
Cyclin F, which is a CRL1 substrate adapter protein encoded by a gene associated to fALS, binds to the N-terminal region of TDP-43 and mediates its ubiquitination in vitro (389). Remarkably, one of cyclin F ALS-associated mutation (S621G) leads to an increase of K48-linked ubiquitin ...
as well as its size and charge, contributing to the decreased shuttling into the nucleus [73,74,75]. Ubiquitin commonly binds to proteins to target them for eventual degradation. Lys-84, one of the multiple TDP-43 ubiquitination sites, is reported to be involved in the nuclear import of TD...
protein aggregation protein phosphorylation ubiquitylation (ubiquitination) mass spectrometry (MS) site-directed mutagenesis amyotrophic lateral sclerosis (ALS) (Lou Gehrig disease) neurodegeneration frontotemporal dementia TDP-43 Introduction The TAR DNA-binding protein of 43 kDa (TDP-43) is the main protei...
and it has been shown that the C-terminal domain is intrinsically prone to aggregation. Mutations in the C-terminal region of the TDP43 gene have been associated with both ALS and FTLD, and are thought to facilitate ubiquitination and phosphorylation of the TDP43 protein, leading to the format...
In addition, ubiquitination of substrates is usually required for substrate incorporation into LEs via ESCRT protein function64. Thus, accumulation of ubiquitinated TDP-43 could indicate endocytic defects, rather than autophagic/proteasomal defects as is commonly assumed. Finally, TDP-43 aggregates do ...
(FTLD).Itisidentiedasa regulatorofessentialtranscriptionaleventsintheCNS,whichisinvolvedinpre-mRNAsplicing,RNAstabilityand transport.InaffectedneuronsoftransgenicrodentmodelswithTDP-43mutationoroverexpression,nuclearand cytoplasmicTDP-43aggregateswithubiquitinationorphosphorylation,andcellcyclesalsoalterate.Hereresearch ...
In affected neurons of transgenic rodent models with TDP-43 mutation or overexpression, nuclear and cytoplasmic TDP-43 aggregates with ubiquitination or phosphorylation, and cell cycles also alterate. Here research progress on transgenic rodent models made by TDP-43 mutation or overexpression is ...
cytoplasmicTDP一43aggregateswithubiquitinationorphosphorylation,andcellcyclesalsoalterate.Hereresearch progressontransgenicrodentmodelsmadebyTDP-43mutationoroverexpressionisreviewedtoexploremolecular mechanisms,pathologicalchangesandnewtherapiesforneurodegenerativedisease. ...