Abstract
Proline directed phosphorylation is a key regulatory mechanism controlling the function of fundamental proteins involved in cell proliferation and oncogenic transformation. Recently, the identification of the phosphorylation dependent prolyl isomerase Pin1 has uncovered a distinct regulatory mechanism controlling protein function. Specifically, Pin1 controls the conversion of peptidyl proline bond conversion from cis to trans, only when the preceding serine or threonine is phosphorylated. The intrinsic inter-conversion of such bonds is rather slow and is further inhibited by phosphorylation. As a consequence catalysis by Pin1 is required to overcome this restriction. Importantly, structural evidence has now demonstrated that Pin1-catalyzed prolyl isomerization can have significant effects on the global structure of substrate proteins. Furthermore, Pin1 overexpression is found in several types of cancer where it functions to not only promote tumorigenesis induced by oncogenes such as Ras and Neu, but also to regulate molecules that facilitate persistent proliferative capacity. Consequently, Pin1-mediated phosphorylation-dependent isomerization represents a unique regulatory mechanism in cell signaling whose deregulation during tumorigenesis adds to the pro-proliferative capacity of tumor cells and therefore Pin1 represents a novel tumor marker and potential therapeutic target.
Keywords: anaphase-promoting complex, Pin1 expression, cyclin D1, Hepatitis B virus, WW domain, Nuclear Magnetic resonance
Current Cancer Drug Targets
Title: Phosphorylation-Specific Prolyl Isomerase Pin1 as a new Diagnostic and Therapeutic Target for Cancer
Volume: 8 Issue: 3
Author(s): Greg Finn and Kun Ping Lu
Affiliation:
Keywords: anaphase-promoting complex, Pin1 expression, cyclin D1, Hepatitis B virus, WW domain, Nuclear Magnetic resonance
Abstract: Proline directed phosphorylation is a key regulatory mechanism controlling the function of fundamental proteins involved in cell proliferation and oncogenic transformation. Recently, the identification of the phosphorylation dependent prolyl isomerase Pin1 has uncovered a distinct regulatory mechanism controlling protein function. Specifically, Pin1 controls the conversion of peptidyl proline bond conversion from cis to trans, only when the preceding serine or threonine is phosphorylated. The intrinsic inter-conversion of such bonds is rather slow and is further inhibited by phosphorylation. As a consequence catalysis by Pin1 is required to overcome this restriction. Importantly, structural evidence has now demonstrated that Pin1-catalyzed prolyl isomerization can have significant effects on the global structure of substrate proteins. Furthermore, Pin1 overexpression is found in several types of cancer where it functions to not only promote tumorigenesis induced by oncogenes such as Ras and Neu, but also to regulate molecules that facilitate persistent proliferative capacity. Consequently, Pin1-mediated phosphorylation-dependent isomerization represents a unique regulatory mechanism in cell signaling whose deregulation during tumorigenesis adds to the pro-proliferative capacity of tumor cells and therefore Pin1 represents a novel tumor marker and potential therapeutic target.
Export Options
About this article
Cite this article as:
Finn Greg and Lu Ping Kun, Phosphorylation-Specific Prolyl Isomerase Pin1 as a new Diagnostic and Therapeutic Target for Cancer, Current Cancer Drug Targets 2008; 8 (3) . https://dx.doi.org/10.2174/156800908784293622
DOI https://dx.doi.org/10.2174/156800908784293622 |
Print ISSN 1568-0096 |
Publisher Name Bentham Science Publisher |
Online ISSN 1873-5576 |
Call for Papers in Thematic Issues
Advances in Cancer Biomarkers and Potential Drug Targets: From Diagnosis to Therapy
Cancer biomarkers play a crucial role in the diagnosis, prognosis, and treatment of cancer. They provide valuable information for cancer detection, risk assessment, treatment selection, and monitoring response to therapy. With advancements in molecular biology and high-throughput technologies, there has been an increasing interest in identifying and characterizing cancer biomarkers ...read more
Novel Therapeutic Approaches to Target Drug Resistant Tumors
With the development of disciplines such as chemical biology and molecular biology, the genes or proteins closely related to tumor occurrence and development have gradually become clear. Targeted therapies targeting these genes or proteins provide more effective methods for tumor treatment. Tumor targeted drugs generally only act on specific targets ...read more
ROLE OF IMMUNE AND GENOTOXIC RESPONSE BIOMARKERS IN TUMOR MICROENVIRONMENT IN CANCER DIAGNOSIS AND TREATMENT
Biological biomarkers have been used in medical research as an indicator of a normal or abnormal process inside the body, or of a disease. Nowadays, various researchers are in process to explore and investigate the biological markers for the early assessment of cancer. DNA Damage response (DDR) pathways and immune ...read more
Targeting the battlefield between host and tumor: basic research and clinical practice on reshaping tumor immune microenvironment
Immune system protects host against malignant tumors through effector cells and molecules. Cancer development and its response to therapy are regulated by inflammation, which either promotes or suppresses cancer progression. Chronic inflammation facilitates cancer progression and treatment resistance, whereas induction of acute inflammatory reactions often lead to anti-cancer immune responses. ...read more
- Author Guidelines
- Graphical Abstracts
- Fabricating and Stating False Information
- Research Misconduct
- Post Publication Discussions and Corrections
- Publishing Ethics and Rectitude
- Increase Visibility of Your Article
- Archiving Policies
- Peer Review Workflow
- Order Your Article Before Print
- Promote Your Article
- Manuscript Transfer Facility
- Editorial Policies
- Allegations from Whistleblowers
Related Articles
-
Overview of Current Immunotherapies Targeting Mutated KRAS Cancers
Current Topics in Medicinal Chemistry Importance of Kier-Hall Topological Indices in the QSAR of Anticancer Drug Design
Current Computer-Aided Drug Design Cholinergic Receptors as Target for Cancer Therapy in a Systems Medicine Perspective
Current Molecular Medicine Ribosomal Proteins and Colorectal Cancer
Current Genomics Feasibility of FDG PET in Inflammatory Bowel Disease
Current Molecular Imaging (Discontinued) The Multiple Pharmaceutical Potential of Curcumin in Parkinson's Disease
CNS & Neurological Disorders - Drug Targets Marine Actinomycetes-derived Natural Products
Current Topics in Medicinal Chemistry Genetic and Modifying Factors that Determine the Risk of Brain Tumors
Central Nervous System Agents in Medicinal Chemistry Antitumor Activity of Zinc Nanoparticles Synthesized with Berberine on Human Epithelial Colorectal Adenocarcinoma (Caco-2) Cells through Acting on Cox-2/NF-kB and p53 Pathways
Anti-Cancer Agents in Medicinal Chemistry The SCF-type E3 Ubiquitin Ligases as Cancer Targets
Current Cancer Drug Targets Antineoplastic Activity of Monocrotaline Against Hepatocellular Carcinoma
Anti-Cancer Agents in Medicinal Chemistry Polypharmacological Properties and Therapeutic Potential of β-Caryophyllene: A Dietary Phytocannabinoid of Pharmaceutical Promise
Current Pharmaceutical Design Evaluation of the Anticancer Activities of the Plant Alkaloids Sanguinarine and Chelerythrine in Human Breast Adenocarcinoma Cells
Anti-Cancer Agents in Medicinal Chemistry Evaluation of Anti-cancer Activity of Stilbene and Methoxydibenzo[b,f] oxepin Derivatives
Current Cancer Drug Targets COX-2, Cell Proliferation and PMA in Head-and-Neck Cancer Cells
Immunology, Endocrine & Metabolic Agents in Medicinal Chemistry (Discontinued) Pharmacokinetics-based Dose Management of 5-Fluorouracil Clinical Research in Advanced Colorectal Cancer Treatment
Mini-Reviews in Medicinal Chemistry 3-Bromopyruvate: A New Targeted Antiglycolytic Agent and a Promise for Cancer Therapy
Current Pharmaceutical Biotechnology A Critical Reappraisal of Off-Label Indications for Topical Photodynamic Therapy with Aminolevulinic Acid and Methylaminolevulinate
Reviews on Recent Clinical Trials γ-Secretase Substrates and their Implications for Drug Development in Alzheimer's Disease
Current Topics in Medicinal Chemistry Overview of Systems Biology and Omics Technologies
Current Medicinal Chemistry