Navigation Links
New binding target for oncogenic viral protein

The DNA tumor virus simian virus 40 produces the Large T antigen which inactivates two of the cell's most important cancer-preventing proteins, p53 and pRb. In a study published in the Journal of Biological Chemistry, researchers at the Fred Hutchinson Cancer Research Center report the discovery of an additional target for T antigen--a protein called Fbw7.

The Fbw7 gene is located in a chromosomal region that is deleted in up to 30% of human tumors. "Fbw7 is itself an important tumor suppressor which makes it an attractive choice for inactivation by Large T," explained Dr. Markus Welcker, the study's first author.

The research appears as the "Paper of the Week" in the March 4 issue of the Journal of Biological Chemistry, an American Society for Biochemistry and Molecular Biology journal.

DNA tumor viruses proliferate by hijacking their host cell's DNA replication machinery. In order to do this, they have evolved mechanisms to override normal cellular replication controls. Simian virus 40 (SV40) accomplishes this task by producing the highly oncogenic large T antigen. This protein corrupts the cellular checkpoint mechanisms that guard cell division and the transcription, replication and repair of DNA. T antigen also inactivates some of the most important proteins that protect cells against malignant transformation, including tumor suppressor proteins p53 and pRb.

In the Journal of Biological Chemistry paper, Dr. Welcker and Dr. Bruce Clurman report that T antigen also binds to another tumor suppressor, Fbw7. This protein is part of a ubiquitin ligase complex that adds ubiquitin to proteins to mark them for destruction by the cell. Fbw7 recognizes a destruction signal on certain proteins that need to be degraded and brings them in close proximity to the enzymes that attach ubiquitin. The proteins recognized by Fbw7 play key roles in cell division, cell growth, differentiation, and cell death.

"These proteins are also some of the most broadly acting cellular oncogenes, and include cyclin E, c-Myc, Notch, and c-Jun," noted Dr. Clurman. "When Fbw7 is mutated in cancers, deregulation of these oncogenic Fbw7 targets is thought to contribute to cancer. SV40 T antigen contains a motif that mimics the destruction signal found in these proteins." However, unlike the other substrates recognized by Fbw7, T antigen is not destroyed by the cell.

Drs. Clurman and Welcker suspect that by acting as a decoy and binding to Fbw7, T antigen protects cellular Fbw7 targets that facilitate viral replication and tumorigenesis.

"I think this work underlines the importance of Fbw7 as an emerging tumor suppressor and the consequences of its loss in tumors," Dr. Welcker emphasized.

"The study of DNA tumors viruses has been an extremely important tool in understanding the cellular pathways that regulate cell division and are disrupted in cancer. Understanding the mechanisms through which these viruses interact with the cellular machinery that regulates cell division may lead to new insights into the pathways that cause cancer. This is an important step to designing new cancer treatment strategies that target these pathways," concluded Dr. Clurman.


Source:American Society for Biochemistry and Molecular Biology

Related biology news :

1. Ancient olfaction protein is shared by many bugs, offering new pest control target
2. A bacterial genome reveals new targets to combat infectious disease
3. Muscle-targeted gene therapy reverses rare muscular dystrophy in mice
4. Researchers identify target for cancer drugs
5. Study reveals candidate targets for anti-retroviral therapeutics
6. MUHC researchers make cancer target breakthrough
7. Future diabetes drugs may target new protein interaction
8. Smart drug targets deadly brain cancer
9. NHGRI targets 12 more organisms for genome sequencing
10. While on trail of dioxin, scientists pinpoint cancer target of green tea
11. Moffitt-USF head toward first human trials of anti-cancer drug that targets protein AKT
Post Your Comments:

(Date:10/29/2015)... , Oct. 29, 2015  Rubicon Genomics, Inc., ... U.S. distribution of its DNA library preparation products, ... Rubicon,s new ThruPLEX Plasma-seq kit. ThruPLEX Plasma-seq has ... preparation of NGS libraries for liquid biopsies--the analysis ... and prognostic applications in cancer and other conditions. ...
(Date:10/27/2015)... -- In the present market scenario, security is one ... verticals such as banking, healthcare, defense, electronic gadgets, and ... secure & simplified access control and growing rate of ... bank accounts, misuse of users, , and so on. ... and smartphones are expected to provide potential opportunities for ...
(Date:10/26/2015)... and LAS VEGAS , Oct. ... Labs , an innovator in modern authentication and a ... announced the launch of its latest version of the ... enabling organizations to use standards-based authentication that supports existing ... S3 Authentication Suite is ideal for organizations deploying customer-facing ...
Breaking Biology News(10 mins):
(Date:11/27/2015)... PA (PRWEB) , ... November 27, 2015 , ... ... Technical Program that includes over 2,000 technical presentations offered in symposia, oral ... chemistry and applied spectroscopy, covers a wide range of applications such as, but ...
(Date:11/26/2015)... MUMBAI , November 26, 2015 ... --> Accutest Research ... accredited Contract Research Organization (CRO), has ... Chase Cancer Center - Temple Health ... ,     (Photo: ) ...
(Date:11/25/2015)... , November 26, 2015 ... Global Biobanking Market 2016 - 2020 report analyzes ... maintaining integrity and quality in long-term samples, minimizing ... long-term cost-effectiveness. Automation minimizes manual errors such as ... technical efficiency. Further, it plays a vital role ...
(Date:11/25/2015)... -- 2 nouvelles études permettent d , ... entre les souches bactériennes retrouvées dans la plaque ... . Ces recherches  ouvrent une nouvelle voie ... efficace de l,un des problèmes de santé les ...    --> 2 nouvelles études permettent d ...
Breaking Biology Technology: