Related Experiment Video

Updated: Jun 5, 2026

Assessing Cellular Target Engagement by SHP2 (PTPN11) Phosphatase Inhibitors
08:45

Assessing Cellular Target Engagement by SHP2 (PTPN11) Phosphatase Inhibitors

Published on: July 17, 2020

Targeting tyrosine phosphorylation of PCNA inhibits prostate cancer growth

Huajun Zhao1, Yuan-Hung Lo, Li Ma

  • 1Corresponding Author: Shao-Chun Wang, Department of Cancer and Cell Biology, 3125 Eden Ave., Cincinnati, OH 45267, USA.

Molecular Cancer Therapeutics
|January 12, 2011
PubMed

Insights

Phosphorylation of proliferation cell nuclear antigen (PCNA) at tyrosine 211 (Y211) is frequent in prostate cancer. Inhibiting Y211 phosphorylation with a peptide halts cancer cell growth and reduces tumor size, suggesting a new therapeutic target.

Area of Science:

  • Oncology
  • Molecular Biology
  • Biochemistry

Background:

  • Proliferation cell nuclear antigen (PCNA) is crucial for DNA replication in cancer cells.
  • Targeting PCNA directly is challenging due to a lack of suitable sites.
  • PCNA phosphorylation at tyrosine 211 (Y211) is vital for its proliferative function in chromatin-associated states.

Purpose of the Study:

  • To investigate the prevalence of Y211 phosphorylation in advanced prostate cancer.
  • To evaluate the therapeutic potential of inhibiting Y211 phosphorylation for prostate cancer treatment.

Main Methods:

  • Utilized a synthetic Y211F peptide designed to inhibit endogenous PCNA Y211 phosphorylation.
  • Assessed peptide efficacy through in vitro studies on human prostate cancer cell lines, including cell cycle analysis and apoptosis assays.
  • Evaluated in vivo efficacy using PC3-derived xenograft models in nude mice.

Main Results:

  • Y211 phosphorylation of PCNA is a common occurrence in advanced prostate cancer.
  • Treatment with the Y211F peptide induced S-phase arrest, inhibited DNA synthesis, and promoted cell death in prostate cancer cell lines.
  • The Y211F peptide significantly reduced tumor growth in vivo.

Conclusions:

  • PCNA phosphorylation at Y211 is a frequent and functionally significant event in prostate cancer.
  • Inhibiting PCNA Y211 phosphorylation represents a potential therapeutic strategy for prostate cancer, including hormone-refractory and advanced forms.

More Related Videos

An Orthotopic Murine Model of Human Prostate Cancer Metastasis06:48

An Orthotopic Murine Model of Human Prostate Cancer Metastasis

Published on: September 18, 2013

MR Molecular Imaging of Prostate Cancer with a Small Molecular CLT1 Peptide Targeted Contrast Agent06:54

MR Molecular Imaging of Prostate Cancer with a Small Molecular CLT1 Peptide Targeted Contrast Agent

Published on: September 3, 2013

Related Concept Videos

Targeted Cancer Therapies02:57

Targeted Cancer Therapies

The targeted cancer therapies, also known as “molecular targeted therapies,” take advantage of the molecular and genetic differences between the cancer cells and the normal cells. It needs a thorough understanding of the cancer cells to develop drugs that can target specific molecular aspects that drive the growth, progression, and spread of cancer cells without affecting the growth and survival of other normal cells in the body.
There are several types of targeted therapies against specific...
mTOR Signaling and Cancer Progression03:03

mTOR Signaling and Cancer Progression

The mammalian target of rapamycin or mTOR protein was discovered in 1994 due to its direct interaction with rapamycin. The protein gets its name from a yeast homolog called TOR. The mTOR protein complex in mammalian cells plays a major role in balancing anabolic processes such as the synthesis of proteins, lipids, and nucleotides and catabolic processes, such as autophagy in response to environmental cues, such as availability of nutrients and growth factors.
The mTOR pathway or the...
Inhibition of Cdk Activity02:34

Inhibition of Cdk Activity

The orderly progression of the cell cycle depends on the activation of Cdk protein by binding to its cyclin partner. However, the cell cycle must be restricted when undergoing abnormal changes. Most cancers correlate to the deregulated cell cycle, and since Cdks are a central component of the cell cycle, Cdk inhibitors are extensively studied to develop anticancer agents. For instance, cyclin D associates with several Cdks, such as Cdk 4/6, to form an active complex. The cyclin D-Cdk4/6 complex...
Inhibition of CDK Activity02:34

Inhibition of CDK Activity

The orderly progression of the cell cycle depends on the activation of Cdk protein by binding to its cyclin partner. However, the cell cycle must be restricted when undergoing abnormal changes. Most cancers correlate to the deregulated cell cycle, and since Cdks are a central component of the cell cycle, Cdk inhibitors are extensively studied to develop anticancer agents. For instance, cyclin D associates with several Cdks, such as Cdk 4/6, to form an active complex. The cyclin D-Cdk4/6 complex...
Abnormal Proliferation02:23

Abnormal Proliferation

Under normal conditions, most adult cells remain in a non-proliferative state unless stimulated by internal or external factors to replace lost cells. Abnormal cell proliferation is a condition in which the cell's growth exceeds and is uncoordinated with normal cells. In such situations, cell division persists in the same excessive manner even after cessation of the stimuli, leading to persistent tumors. The tumor arises from the damaged cells that replicate to pass the damage to the daughter...
PI3K/mTOR/AKT Signaling Pathway01:22

PI3K/mTOR/AKT Signaling Pathway

The mammalian target of rapamycin  (mTOR) is a serine/threonine kinase that regulates growth, proliferation, and cell survival in response to hormones, growth factors, or nutrient availability. This kinase exists in two structurally and functionally distinct forms: mTOR complex 1  (mTORC1) and mTOR complex 2  (mTORC2). The first form (mTORC1) is composed of a rapamycin-sensitive Raptor and proline-rich Akt substrate, PRAS40. In contrast,  mTORC2 consists of a rapamycin-insensitive companion...