The Anticancer Activity of a First-in-class Small-molecule Targeting PCNA
Abstract
Proliferating cell nuclear antigen (PCNA) plays an essential role in regulating DNA synthesis and repair and is indispensable to cancer cell growth and survival. We previously reported a novel cancer associated PCNA isoform (dubbed caPCNA), which was ubiquitously expressed in a broad range of cancer cells and tumor tissues, but not significantly in nonmalignant cells. We found the L126-Y133 region of caPCNA is structurally altered and more accessible to protein–protein interaction. A cell-permeable peptide harboring the L126-Y133 sequence blocked PCNA interaction in cancer cells and selectively kills cancer cells and xenograft tumors. On the basis of these findings, we sought small molecules targeting this peptide region as potential broad-spectrum anticancer agents.
Document Details
- Document Type
- Pub Defense Publication
- Publication Date
- Dec 01, 2018
- Source ID
- 10.1158/1078-0432.ccr-18-0592
Entities
People
- David Horne
- Emily Sun
- Fumiko Yakushijin
- Hongzhi Li
- Jeremy M. Stark
- Jianfei Chao
- Karen L. Reckamp
- Linda H. Malkas
- Long Gu
- Qi Cui
- Robert J. Hickey
- Robert Lingeman
- Steven L. Vonderfecht
- Timothy W. Synold
- Weidong Hu
- Yanhong Shi
- Yate-ching Yuan
- Yuan Chen
Organizations
- City of Hope National Medical Center
- National Institutes of Health
- United States Department of Defense