# Retinal degeneration protein 3 mutants are associated with cell-cycle arrest and apoptosis

## TL;DR

This study explores how mutations in the RD3 protein affect cell survival and death, revealing its role in cancer development.

## Contribution

The study identifies new functional mechanisms of RD3 mutants in cell-cycle arrest and apoptosis, linking them to tumor growth.

## Key findings

- RD3 is downregulated in glioblastoma compared to non-tumor tissues.
- RD3 overexpression decreases cell viability, causing G2/M phase arrest and apoptosis.
- Single-point mutations in RD3 reduce its impact on cell survival and death.

## Abstract

Retinal degeneration protein 3 (RD3) plays a crucial role in controlling guanylate cyclase activity in photoreceptor rod and cone cells, and mediates trafficking processes within photoreceptor cells. Loss of RD3 function correlates with severe forms of retinal dystrophy and the development of aggressive neuroblastoma cancer. In the present study, we analyzed RD3 expression in glioblastoma in comparison to non-tumor tissue using public databases and qRT-PCR. We found that RD3 is downregulated in glioblastoma compared to non-tumor tissues. To better understand the cellular function of RD3 in the context of tumor development, we performed first functional cell culture studies to clarify a possible involvement of RD3 in cell survival and the cell cycle. Interestingly, RD3 overexpression significantly decreased cell viability, which subsequently led to cell-cycle arrest at the G2/M phase and induced cell apoptosis. Conversely, single-point mutations in RD3 at the exposed protein surface involved in RD3-target interaction diminished the impact of RD3. Therefore, a controlled RD3 expression level seems to be important for a balance of cell death and cell survival rate. These new functional mechanisms of RD3 expression could help in understanding tumor development and growth