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Copyright ©The Author(s) 2020. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Immunol. May 27, 2020; 10(1): 1-12
Published online May 27, 2020. doi: 10.5411/wji.v10.i1.1
PICOT promotes T lymphocyte proliferation by down-regulating cyclin D2 expression
Pinakin Pandya, Noah Isakov
Pinakin Pandya, Noah Isakov, The Shraga Segal Department of Microbiology, Immunology and Genetics, Faculty of Health Sciences and the Cancer Research Center, Ben Gurion University of the Negev, Beer Sheva 84105, Israel
Pinakin Pandya, Department of Computational and System biology, UPMC Hillman Cancer Center, University of Pittsburgh, School of Medicine, Pittsburgh, PA 15232, United States
Author contributions: This manuscript was written and edited by both authors.
Supported by the USA-Israel Binational Science Foundation, No. 2013034; the Israel Science Foundation administered by the Israel Academy of Science, No. 1235/17; the Jacki and Bruce Barron Cancer Research Scholars’ Program, City of Hope and the Israel Cancer Research Fund, No. 87735611.
Conflict-of-interest statement: The authors have no financial conflicts of interest.
Open-Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
Corresponding author: Noah Isakov, PhD, Professor, The Shraga Segal Department of Microbiology, Immunology and Genetics, Faculty of Health Sciences and the Cancer Research Center, Ben Gurion University of the Negev, P.O.B. 653, Beer Sheva 84105, Israel. noah@bgu.ac.il
Received: January 25, 2020
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
Processing time: 122 Days and 16 Hours
Abstract

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.

Keywords: Protein kinase C-interacting cousin of thioredoxin; Glutaredoxin 3; Cyclin D2; Histone methylation; T lymphocyte; Histone 3 lysine 27 trimethylation

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.