An elongated tract of polyQ in the carboxyl ‑terminus of human α1A calcium channel induces cell apoptosis by nuclear translocation.

An elongated tract of polyQ in the carboxyl‑terminus of human α1A calcium channel induces cell apoptosis by nuclear translocation. Oncol Rep. 2020 Jul;44(1):156-164 Authors: Sun J, Sun X, Li Z, Ma D, Lv Y Abstract 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 ma...
Source: Oncology Reports - Category: Cancer & Oncology Tags: Oncol Rep Source Type: research