home   genetic news   bioinformatics   biotechnology   literature   journals   ethics   positions   events   sitemap
 
  HUM-MOLGEN -> Genetic News | search  
 

The Flip Side of p27

 
  July, 15 2007 6:13
your information resource in human molecular genetics
 
     
In a paper published online ahead of its July 15th print date in Genes and Development, Dr. James Roberts (FHCRC) and colleagues reveal a surprising new role for the p27 tumor suppressor in tumors and stem cells. “p27 is one of most frequently misregulated proteins in human cancers, and this is strongly predictive of an aggressive tumor phenotype,” explains Dr. Roberts.

Their finding, along with the novel animal model they studied, hold great promise for furthering understanding of how abnormal expression of p27 contributes to cancer growth and the rational design of drugs to combat p27 dysfunction.

p27 is a cell cycle regulator ¬ more specifically a cyclin-dependent kinase (CDK) inhibitor -- meaning that it can inactivate cyclin-CDK protein complexes and specific CDK enzymes essential for cell division cause cell cycle arrest in the G1 phase of cell growth and thereby stop cell proliferation. p27 is thus a CDK-dependent tumor suppressor: Its inactivation promotes uncontrolled cell growth.

As published previously, p27-kockout mice (mice completely lacking p27) display multi-organ hyperplasia and pituitary tumors. But is has been a mystery as to why the p27 knockout mouse failed to recapitulate the widespread and potent role that p27 has in human cancer.

Dr. Roberts and colleagues generated a new strain of p27-mutant mice: p27 that cannot bind to cyclin-CDK, but otherwise functions normally. These p27CK- mice, as they are known, enabled researchers to probe the CDK-independent functions of p27. What they found was “totally unexpected,” according to Dr. Roberts.

As it turned out, p27 has a strong CDK-independent oncogenic effect. Unlike the p27-null mice, p27CK- mice developed aggressive spontaneous tumors in multiple, diverse organs. Furthermore, the tumors of the lungs and retina were associated with an expansion of the stem cell populations of these tissues. Thus, p27 can function as a CDK-dependent tumor suppressor, as well as a CDK-independent oncogene.

Comparison of the p27CK- and p27-null phenotypes led the researchers to conclude that the p27CK- mice may, in fact, represent a more faithful model of the dual role of p27 in human tumorigenesis. Dr. Roberts says that the p27CK- mouse not only eliminates the tumor suppressing function of p27, but also liberates its oncogenic activity, thus allowing its full effect on tumorigenesis to be revealed.


Source: Genes and Development Press Release


Message posted by: Robin Kimmel

print this article mail this article
Bookmark and Share this page (what is this?)

Social bookmarking allows users to save and categorise a personal collection of bookmarks and share them with others. This is different to using your own browser bookmarks which are available using the menus within your web browser.

Use the links below to share this article on the social bookmarking site of your choice.

Read more about social bookmarking at Wikipedia - Social Bookmarking

Latest News
Variants Associated with Pediatric Allergic Disorder

Mutations in PHF6 Found in T-Cell Leukemia

Genetic Risk Variant for Urinary Bladder Cancer

Antibody Has Therapeutic Effect on Mice with ALS

Regulating P53 Activity in Cancer Cells

Anti-RNA Therapy Counters Breast Cancer Spread

Mitochondrial DNA Diversity

The Power of RNA Sequencing

‘Pro-Ageing' Therapy for Cancer?

Niche Genetics Influence Leukaemia

Molecular Biology: Clinical Promise for RNA Interference

Chemoprevention Cocktail for Colon Cancer

more news ...

Generated by News Editor 2.0 by Kai Garlipp
WWW: Kai Garlipp, Frank S. Zollmann.
7.0 © 1995-2017 HUM-MOLGEN. All rights reserved. Liability, Copyright and Imprint.