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
-
Novel Marine-Derived Anti-Cancer Agents
Current Pharmaceutical Design The Urokinase Receptor in the Central Nervous System
CNS & Neurological Disorders - Drug Targets Determination of Dysregulated miRNA Expression Levels by qRT-PCR after the Application of Usnic Acid to Breast Cancer
Anti-Cancer Agents in Medicinal Chemistry Reactive Oxygen Species: Physiological Roles in the Regulation of Vascular Cells
Current Molecular Medicine Modern drug delivery systems for targeting the posterior segment of the eye
Current Pharmaceutical Design Hitting the Golden TORget: Curcumin’s Effects on mTOR Signaling
Anti-Cancer Agents in Medicinal Chemistry Indoleamine 2,3-Dioxygenase, an Emerging Target for Anti-Cancer Therapy
Current Cancer Drug Targets Vitamins for Cancer Prevention and Treatment: An Insight
Current Molecular Medicine Perfusion Computed Tomography and its Application in Oncologic Practice
Current Molecular Imaging (Discontinued) Selective Cyclooxygenase-2 Inhibitors and Non-small Cell Lung Cancer
Current Medicinal Chemistry Analysis of Simple Sequence Repeats in Mammalian Cell Cycle Genes
Recent Advances in DNA & Gene Sequences (Discontinued) Candida Infections and Human Defensins
Protein & Peptide Letters Gene Expression Abnormalities in Thymoma
Current Pharmacogenomics Inflammasome, Inflammation and Cancer: An Interrelated Pathobiological Triad
Current Drug Targets Treatment of Nasopharyngeal Carcinoma: Therapeutic Management and Future View of Epstein-Barr Virus-Targeting Treatment
Current Cancer Therapy Reviews Modulation of Anxiety Behavior by Intranasally Administered Vaccinia Virus Complement Control Protein and Curcumin in a Mouse Model of Alzheimers Disease
Current Alzheimer Research Natural Products As Antimitotic Agents
Current Topics in Medicinal Chemistry Advancing Drug Therapy for Brain Tumours: A Current Review of the Pro-inflammatory Peptide Substance P and its Antagonists as Anti-cancer Agents
Recent Patents on CNS Drug Discovery (Discontinued) Pleiotrophin as a Possible New Target for Angiogenesis-Related Diseases and Cancer
Recent Patents on Anti-Cancer Drug Discovery A Review of Gene Expression Profiling of Human Embryonic Stem Cell Lines and their Differentiated Progeny
Current Stem Cell Research & Therapy