An elongated tract of polyQ in the carboxyl-terminus of human α1A calcium channel induces cell apoptosis by nuclear translocation
| Autor: | Dihui Ma, Ji Sun, Yudan Lv, Zhuo Li, Xiguang Sun |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2020 |
| Předmět: |
0301 basic medicine
Cancer Research Cell Survival Poly ADP ribose polymerase Cell Mutant nuclear translocation Active Transport Cell Nucleus CACNA1A 03 medical and health sciences Neuroblastoma 0302 clinical medicine Cell Line Tumor Exome Sequencing medicine Humans Polymerase Cell Proliferation biology Oncogene cell apoptosis Chemistry Cell growth Caspase 3 General Medicine Articles Cell cycle Myoclonic Epilepsies Progressive Cell biology 030104 developmental biology medicine.anatomical_structure Oncology Apoptosis 030220 oncology & carcinogenesis Mutation biology.protein Calcium Channels Poly(ADP-ribose) Polymerases Peptides polyglutamine Signal Transduction |
| Zdroj: | Oncology Reports |
| ISSN: | 1791-2431 1021-335X |
| Popis: | An aberrant elongated tract of glutamine residues (polyQ) in proteins induces multiple diseases treated in the clinic. In our previous study of progressive myoclonic epilepsy (PME), using whole‑exome sequencing, a mutant Cav2.1 protein with an aberrant elongated polyQ tract was identified in PME patients. To investigate the molecular mechanism and cell biology of this aberrant elongated polyQ tract, wild‑type Cav2.1 with 13 polyQ repeats (Cav2.1 wt‑Q13) and mutant‑type Cav2.1 with 26 polyQ repeats (Cav2.1 mt‑Q26) were prepared and introduced into human SH‑SY5Y neuroblastoma cells. Using a WST‑1 assay, it was revealed that Cav2.1 mt‑Q26 markedly suppressed the proliferation of the SH‑SY5Y cells, a result not observed for the Cav2.1 wt‑Q13‑transfected cells. It was also revealed that Cav2.1 mt and its truncated molecules suppressed cell proliferation by inducing apoptosis rather than arresting the cell cycle. Further investigations indicated a nuclear translocation phenomenon associated with the Cav2.1 mt molecules. Mechanistically, it was revealed that the Cav2.1 mt molecules activated the Bcl‑2/Bax, caspase‑3 and poly ADP‑ribose polymerase (PARP) apoptotic pathways. The present study may provide new insights for interpreting the pathogenesis of PME and the relationship among polyQ, CACNA1A gene mutations and PME. |
| Databáze: | OpenAIRE |
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