Published online May 27, 2020. doi: 10.5411/wji.v10.i1.1
Peer-review started: January 25, 2020
First decision: April 19, 2020
Revised: May 9, 2020
Accepted: May 12, 2020
Article in press: May 12, 2020
Published online: May 27, 2020
The mammalian protein kinase C-interacting cousin of thioredoxin (PICOT; also termed glutaredoxin 3) is a multi-domain monothiol glutaredoxin that is involved in a wide variety of signaling pathways and biological processes. PICOT is required for normal and transformed cell growth and is critical for embryonic development. Recent studies in T lymphocytes demonstrated that PICOT can translocate to the nucleus and interact with embryonic ectoderm development, a polycomb group protein and a core component of the polycomb repressive complex 2, which contributes to the maintenance of transcriptional repression and chromatin remodeling. Furthermore, PICOT was found to interact with chromatin-bound embryonic ectoderm development and alter the extent of histone 3 lysine 27 trimethylation at the promoter region of selected polycomb repressive complex 2 target genes. PICOT knockdown in Jurkat T cells led to increased histone 3 lysine 27 trimethylation at the promoter region of CCND2, a cell cycle-regulating gene which encodes the cyclin D2 protein. As a result, the expression levels of CCND2 mRNA and protein levels were reduced, concomitantly with inhibition of the cell growth rate. Analysis of multiple data sets from the Cancer Genome Atlas revealed that a high expression of PICOT correlated with a low expression of CCND2 in a large number of human cancers. In addition, this parameter correlated with poor patient survival, suggesting that the ratio between PICOT/CCND2 mRNA levels might serve as a predictor of patient survival in selected types of human cancer.
Core tip: Protein kinase C-interacting cousin of thioredoxin (PICOT) is a cell growth-regulating protein that interacts with embryonic ectoderm development, a core component of the polycomb repressive complex 2. PICOT is able to alter the extent of the tri-methylation of histone 3 lysine 27 at the promoter region of the polycomb repressive complex 2 target gene, CCND2, which encodes the cell cycle-regulating protein, cyclin D2. High expression levels of PICOT correlates with low expression levels of CCND2 and poor survival of a large number of human cancer patients. The results suggest that a high PICOT/CCND2 expression level ratio might serve as a predictor of patient survival in selected types of human cancer.