| MLO | Stress granule |
|---|---|
| Class | MLO-unchanged |
| Synonyms | Stress granules, SGs |
| Classification | nervous system disease |
|---|---|
| Disease | Amyotrophic lateral sclerosis |
| More Disease Information | |
| MLO change | Size: - | Number: - | Assembly: - | ||
|---|---|---|---|---|---|
| Dynamic: - | Others: - | ||||
| Description: - | |||||
| Publication note | We further uncover that PARylation of hnRNP A1 at K298 controls its nucleocytoplasmic transport,whereas PAR-binding via the PAR-binding motif (PBM) of hnRNP A1 regulates its association with stress granules. Moreover, we reveal that PAR not only dramatically enhances the liquid-liquid phase separation of hnRNP A1,but also promotes the co-phase separation of hnRNP A1 and TDP-43 in vitro and their interaction in vivo. Finally,both genetic and pharmacological inhibition of PARP mitigates hnRNP A1- and TDP-43-mediated neurotoxicity in cell and Drosophila models of ALS. Together,our findings suggest a novel and crucial role for PARylation in regulating the dynamics of RNP granules,and that dysregulation in PARylation and PAR levels may contribute to ALS disease pathogenesis by promoting protein aggregation. | ||||
| Organism | Homo sapiens，Mus musculus | Cell line or tissue | HeLa，NSC-34 | ||
| Experiment evidence | Direct experiment | Reference | 30728452 (2019-03-01) | ||
| In vivo PS evidence | FRAP: - | 1,6-hexa treatment: - | Spherical shape: - | ||
| Fusion&Fission: - | PS role: - | ||||
| Mutation | - | Expression change | - |
|---|---|---|---|
| PTM | Position Residue | Modification | Modifying enzyme |
| - | - | - | |
| Description | Mutation: - Expression change: - PTM: PARylation of hnRNP A1 at K298 controls its nucleocytoplasmic transport, whereas PAR-binding via the PAR-binding motif (PBM) of hnRNP A1 regulates its association with stress granules. |
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| Drugs from DrugBank | - | |
|---|---|---|
| Molecules from BindingDB(PubChem CID) | 45223816；121380360；56739767；863；4212；6112 | |
| Molecules from PDBBind | - | |
| Interference Note | - |
| Pscore overall score | 5.95 | PSPer | 0.38 |
|---|---|---|---|
| catGRANULE overall score | 2.04 | R+Y | 0.0018461538000000002 |
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Chao Hou, Haotai Xie, Yang Fu, Yao Ma, Tingting Li. MloDisDB: A manually curated DataBase of the relations between MembraneLess Organelles and DISeases