Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Natural tumor suppressor in body discovered by UCSD medical researchers

01.04.2005


A natural tumor suppressor that could potentially be turned on in certain cancer cells to prevent the formation of tumors has been discovered by researchers at the University of California, San Diego (UCSD) School of Medicine.


Akt/protein kinase B controls the balance between cell survival and cell death. The activated form of this kinase tips the balance towards cell proliferation and survival, whereas the inactive form tips the balance towards programmed cell death, apoptosis. Akt can be inactivated by two mechanisms: the tumor suppressor PTEN pre-empts activation by removing the activating signals, and the tumor suppressor PHLPP terminates activation by directly turning off a key phosphorylation switch on Akt.



Located on chromosome 18 and called PH domain Leucine-rich repeat Protein Phosphatase (PHLPP, pronounced "flip"), the tumor suppressor is described in the April 1, 2005 issue of the journal Molecular Cell. The scientists demonstrated that PHLPP deletes a phosphate molecule, causing termination of cell-growth signaling by a protein called Akt that controls the balance between cell growth leading to cancer and cell death that prevents tumor formation.

A drug that turns on PHLPP, so that it suppresses cell growth caused by Akt, could be a potential cancer therapy," said the study’s senior author, Alexandra C. Newton, Ph.D., UCSD professor of pharmacology. "Currently there are no compounds identified to directly stop Akt from causing cancer growth, once Akt signaling has been initiated."


Scientists have known that Akt is critical in regulating cell growth and death, and that it is linked to some of the most common human cancers. Although one group of scientists discovered a molecule called PTEN*, which prevents activation of Akt, no one to date had determined how to directly turn off Akt once it has been activated.

Since the Akt molecule is locked in the "on" position when it has phosphate on it, the UCSD team reasoned that there must be another molecule that will strip off the phosphate and lock Akt in the "off" position. The scientists conducted a database search of the human genome for a phosphatase, which is an enzyme that acts as a catalyst in regulating cellular processes by removing phosphate molecules. Based on the chemical components of Akt, they specifically looked for a phosphatase linked to the PH domain, a protein module found in a wide variety of chemical signaling proteins in organisms ranging from yeast to humans.

Once they found PHLPP, which they discovered was expressed throughout the body, the scientists used biochemical and cellular studies in human and other mammalian tissue to determine that PHLPP levels are markedly reduced in several colon cancer and gliobastoma human cell lines that had elevated Akt phosphorylation. Reintroduction of PHLPP into the cell lines caused a dramatic suppression of tumor growth. With additional laboratory tests, the team found that PHLPP stops tumor growth by deleting a specific phosphate molecule at a position called Ser473 on Akt.

The scientists noted that PHLPP’s role as a tumor suppressor would apply to all cancers where Akt is elevated, "which is a large number of cancers," Newton said.

Sue Pondrom | EurekAlert!
Further information:
http://www.ucsd.edu

More articles from Life Sciences:

nachricht Nerves control the body’s bacterial community
26.09.2017 | Christian-Albrechts-Universität zu Kiel

nachricht Ageless ears? Elderly barn owls do not become hard of hearing
26.09.2017 | Carl von Ossietzky-Universität Oldenburg

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

Die letzten 5 Focus-News des innovations-reports im Überblick:

Im Focus: The fastest light-driven current source

Controlling electronic current is essential to modern electronics, as data and signals are transferred by streams of electrons which are controlled at high speed. Demands on transmission speeds are also increasing as technology develops. Scientists from the Chair of Laser Physics and the Chair of Applied Physics at Friedrich-Alexander-Universität Erlangen-Nürnberg (FAU) have succeeded in switching on a current with a desired direction in graphene using a single laser pulse within a femtosecond ¬¬ – a femtosecond corresponds to the millionth part of a billionth of a second. This is more than a thousand times faster compared to the most efficient transistors today.

Graphene is up to the job

Im Focus: LaserTAB: More efficient and precise contacts thanks to human-robot collaboration

At the productronica trade fair in Munich this November, the Fraunhofer Institute for Laser Technology ILT will be presenting Laser-Based Tape-Automated Bonding, LaserTAB for short. The experts from Aachen will be demonstrating how new battery cells and power electronics can be micro-welded more efficiently and precisely than ever before thanks to new optics and robot support.

Fraunhofer ILT from Aachen relies on a clever combination of robotics and a laser scanner with new optics as well as process monitoring, which it has developed...

Im Focus: The pyrenoid is a carbon-fixing liquid droplet

Plants and algae use the enzyme Rubisco to fix carbon dioxide, removing it from the atmosphere and converting it into biomass. Algae have figured out a way to increase the efficiency of carbon fixation. They gather most of their Rubisco into a ball-shaped microcompartment called the pyrenoid, which they flood with a high local concentration of carbon dioxide. A team of scientists at Princeton University, the Carnegie Institution for Science, Stanford University and the Max Plank Institute of Biochemistry have unravelled the mysteries of how the pyrenoid is assembled. These insights can help to engineer crops that remove more carbon dioxide from the atmosphere while producing more food.

A warming planet

Im Focus: Highly precise wiring in the Cerebral Cortex

Our brains house extremely complex neuronal circuits, whose detailed structures are still largely unknown. This is especially true for the so-called cerebral cortex of mammals, where among other things vision, thoughts or spatial orientation are being computed. Here the rules by which nerve cells are connected to each other are only partly understood. A team of scientists around Moritz Helmstaedter at the Frankfiurt Max Planck Institute for Brain Research and Helene Schmidt (Humboldt University in Berlin) have now discovered a surprisingly precise nerve cell connectivity pattern in the part of the cerebral cortex that is responsible for orienting the individual animal or human in space.

The researchers report online in Nature (Schmidt et al., 2017. Axonal synapse sorting in medial entorhinal cortex, DOI: 10.1038/nature24005) that synapses in...

Im Focus: Tiny lasers from a gallery of whispers

New technique promises tunable laser devices

Whispering gallery mode (WGM) resonators are used to make tiny micro-lasers, sensors, switches, routers and other devices. These tiny structures rely on a...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

“Lasers in Composites Symposium” in Aachen – from Science to Application

19.09.2017 | Event News

I-ESA 2018 – Call for Papers

12.09.2017 | Event News

EMBO at Basel Life, a new conference on current and emerging life science research

06.09.2017 | Event News

 
Latest News

Nerves control the body’s bacterial community

26.09.2017 | Life Sciences

Four elements make 2-D optical platform

26.09.2017 | Physics and Astronomy

Goodbye, login. Hello, heart scan

26.09.2017 | Information Technology

VideoLinks
B2B-VideoLinks
More VideoLinks >>>