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.
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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 |
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