About My Health Careers Internship MedBlogs Contact us
Medindia LOGIN REGISTER
Advertisement

Little-studied Cellular Mechanism Raised to Potential Drug Target: Scripps Scientists

by Nancy Needhima on December 13, 2011 at 11:15 PM
Font : A-A+

Little-studied Cellular Mechanism Raised to Potential Drug Target: Scripps Scientists

Phosphorylation of proteins has usually been considered as the insertion of a phosphorous group into a protein that turns it on or off according to the factor regulating a range of cellular processes from cell metabolism to programmed cell death. Now, scientists from the Florida campus of The Scripps Research Institute have identified the importance of a novel protein-regulating mechanism -- called sulfenylation -- that is similar to phosphorylation and may, in fact, open up opportunities to develop new types of drugs for diseases such as cancer.

The study was published December 11, 2011, in an advance online edition of the journal Nature Chemical Biology.

Advertisement

"With this paper, we've elevated protein sulfenylation from a marker of oxidative stress to a bona fide reversible post translational modification that plays a key regulatory role during cell signaling," said Kate Carroll, a Scripps Research associate professor who led the study. "The sulfenyl modification is the new kid on the block."

During periods of cellular stress, caused by factors such as exposure to UV radiation or chronic disease states like cancer, the level of highly reactive oxygen-containing molecules can increase, resulting in inappropriate modification of proteins and cell damage. In sulfenylation, one oxidant, hydrogen peroxide, functions as a messenger that can activate cell proliferation through oxidation of cysteine residues in signaling proteins, producing sulfenic acid. Cysteine, an amino acid (natural protein building block), is highly oxidant sensitive.
Advertisement

Conventional wisdom has long held that if hydrogen peroxide does exist in the cell at any appreciable level, it represents a disease state, not a regulatory event. The new study shows that sulfenylation is actually a positive protein modification, and that it's required for signaling through the pathway, a validation of a long-held belief in some scientific circles that hydrogen peroxide functions as a general signaling molecule, not an oxidative "bad boy" to be eliminated at all costs.

A New Chemical Probe

To explore the process, Carroll and her colleagues developed a highly selective chemical probe -- known as DYn-2 -- with the ability to detect minute differences in sulfenylation rates within the cell.

With the new probe, the team was able to show that a key signaling protein, epidermal growth factor receptor (EGFR), is directly modified by hydrogen peroxide at a critical active site cysteine, stimulating its tyrosine kinase activity.

The technology described in the new paper is unique, Carroll said, because it allows scientists to trap and detect these modifications in situ, without interfering with the redox balance of the cell. "Probing cysteine oxidation in a cell lysate is like looking for a needle in a haystack," she said, "our new approach preserves labile sulfenyl modifications and avoids protein oxidation artifacts that arise during cell homogenization."

As with phosphorylation, future studies on sulfenylation will delve into the exciting discovery of new enzymes, new signaling processes, and new mechanisms of regulation.

Another broad impact of these findings, Carroll said, is to open up an entirely new mechanism to exploit for the development of therapeutics, particularly in cancer. "It should influence the design of inhibitors that target oxidant-sensitive cysteine residues in the future," she said.

Source: Eurekalert
Advertisement

Advertisement
News A-Z
A B C D E F G H I J K L M N O P Q R S T U V W X Y Z
Advertisement
News Category
What's New on Medindia
January is the Thyroid Awareness Month in 2022
Menstrual Disorders
Coffee May Help You Fight Endometrial Cancer
View all

Medindia Newsletters Subscribe to our Free Newsletters!
Terms & Conditions and Privacy Policy.

More News on:
Drug Toxicity Signature Drug Toxicity 

Recommended Reading
Phosphorylation of Alpha-synuclein is A Balancing Act in Parkinson's Disease
The neuronal protein alpha-synuclein may play a crucial role in Parkinson's disease, both genetic .....
New Method for Detection of Phosphoproteins Reveals Regulator of Melanoma Invasion
Scientists have developed a new approach for surveying phosphorylation, a process that is regulated ...
Mechanism Behind Initiation Of Plaques In Alzheimer's Brain Identified
A molecular mechanism that triggers initiation of plaques in Alzheimer's brain has been identified ....
Neocortex- A Cache of Memories
PKMzeta , the "memory storage molecule" keeps long-term memories in the neocortex and ....
Drug Toxicity
Drug toxicity is an adverse reaction of the body towards a drug that results as a side effect of a d...

Disclaimer - All information and content on this site are for information and educational purposes only. The information should not be used for either diagnosis or treatment or both for any health related problem or disease. Always seek the advice of a qualified physician for medical diagnosis and treatment. Full Disclaimer

© All Rights Reserved 1997 - 2022

This site uses cookies to deliver our services. By using our site, you acknowledge that you have read and understand our Cookie Policy, Privacy Policy, and our Terms of Use
open close
CONSULT A DOCTOR
I have read and I do accept terms of use - Telemedicine

Advantage Medindia: FREE subscription for 'Personalised Health & Wellness website with consultation' (Value Rs.300/-)