Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Zinc deficiency linked to activation of Hedgehog signaling pathway

17.04.2015

Suggests link with diseases associated with zinc deficiency

Zinc deficiency - long associated with numerous diseases, e.g. autism, lung cancer, prostate cancer, and ovarian cancers - can lead to activation of the Hedgehog signaling pathway, a biomolecular pathway that plays essential roles in developing organisms and in diseases, according to new research at Rensselaer Polytechnic Institute.


Novel mechanism in diseases: zinc deficiency can enhance Hedgehog (Hh) ligand production and activate Hh signal pathway. Zinc deficiency is well known in prostate cancer, lung cancer, ovarian cancer and autism, where Hh activation is also observed, but a mechanistic link between zinc and Hh has never been previously demonstrated.

Credit: RPI

"Hedgehog is critical to normal development, but in adults the pathway, if reactivated, may lead to uncontrolled cell growth and proliferation in cancer," said Chunyu Wang, associate professor in biological sciences at Rensselaer, member of the Center for Biotechnology and Interdisciplinary Studies, and corresponding author of the research.

"Our paper suggests a link between zinc deficiency and activation of the Hedgehog pathway in many diseases where zinc deficiency and Hedgehog activation co-exist."

The paper, titled "Zinc Inhibits Hedgehog Autoprocessing," was recently published online in the Journal of Biological Chemistry, demonstrating that zinc inhibits the activation of the Hedgehog signaling pathway by binding to a section of a precursor protein that activates the pathway.

The Hedgehog pathway is a key regulator of cell growth and development that helps to establish the body plan of all animals with bilateral symmetry. In a critical step that launches Hedgehog signaling, the Hedgehog precursor protein divides itself or "self-cleaves" into two parts: the Hedgehog ligand responsible for signaling, and a catalytic domain responsible for the self-cleavage.

No external catalyst is needed in the autoprocessing reaction, with the Hedgehog catalytic domain acting as the catalyst in the transformation.

Researchers demonstrated that zinc, when present, binds to the active sites of the catalytic domain and inhibits the autoprocessing and therefore, the generation of the Hedgehog ligand. Zinc deficiency is correlated with autism and many cancers; for example, a hallmark of prostate cancer is zinc deficiency in prostate tissue. However, the exact relationship between a lack of zinc and the development of disease is not fully understood.

"Normally, in adults, zinc will inhibit the production of the Hedgehog ligand, and therefore inhibit the Hedgehog pathway," said Wang. "But if there is a zinc deficiency, the pathway can be activated due to enhanced production of Hedgehog ligand. We show that zinc inhibits this autoprocessing reaction from the precursor to the ligand, providing an additional mechanism of how zinc deficiency may promote cancer development.

This is something that nobody else has shown before. Zinc and Hedgehog are essential and extremely versatile biomolecules; linking these two will have profound implications for normal physiology and disease."

The research included testing in vitro and in cell culture using astrocytes (star-shaped cells found in the brain). Using solution NMR, researchers also examined zinc interaction with the Hedgehog catalytic domain, to determine the binding site of zinc -- the specific amino acids within the protein to which the zinc binds.

###

A team of researchers participated in this research, including first author Jian Xie, a fourth-year graduate student in the biochemistry and biophysics graduate program at Rensselaer; the research group of Brian Callahan, assistant professor of chemistry at Binghamton University, at the State University of New York; the group of Leo Wan, assistant professor in the Department of Biomedical Engineering at Rensselaer; and Brigitte Arduini, director of Rensselaer Center for Stem Cell Research in the Center of Biotechnology and Interdisciplinary Studies, among many others.

Media Contact

Mary Martialay
martim12@rpi.edu

 @rpinews

http://news.rpi.edu/ 

Mary Martialay | EurekAlert!

More articles from Life Sciences:

nachricht Researchers uncover protein-based “cancer signature”
05.12.2016 | Universität Basel

nachricht The Nagoya Protocol Creates Disadvantages for Many Countries when Applied to Microorganisms
05.12.2016 | Leibniz-Institut DSMZ-Deutsche Sammlung von Mikroorganismen und Zellkulturen GmbH

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

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

Im Focus: Shape matters when light meets atom

Mapping the interaction of a single atom with a single photon may inform design of quantum devices

Have you ever wondered how you see the world? Vision is about photons of light, which are packets of energy, interacting with the atoms or molecules in what...

Im Focus: Novel silicon etching technique crafts 3-D gradient refractive index micro-optics

A multi-institutional research collaboration has created a novel approach for fabricating three-dimensional micro-optics through the shape-defined formation of porous silicon (PSi), with broad impacts in integrated optoelectronics, imaging, and photovoltaics.

Working with colleagues at Stanford and The Dow Chemical Company, researchers at the University of Illinois at Urbana-Champaign fabricated 3-D birefringent...

Im Focus: Quantum Particles Form Droplets

In experiments with magnetic atoms conducted at extremely low temperatures, scientists have demonstrated a unique phase of matter: The atoms form a new type of quantum liquid or quantum droplet state. These so called quantum droplets may preserve their form in absence of external confinement because of quantum effects. The joint team of experimental physicists from Innsbruck and theoretical physicists from Hannover report on their findings in the journal Physical Review X.

“Our Quantum droplets are in the gas phase but they still drop like a rock,” explains experimental physicist Francesca Ferlaino when talking about the...

Im Focus: MADMAX: Max Planck Institute for Physics takes up axion research

The Max Planck Institute for Physics (MPP) is opening up a new research field. A workshop from November 21 - 22, 2016 will mark the start of activities for an innovative axion experiment. Axions are still only purely hypothetical particles. Their detection could solve two fundamental problems in particle physics: What dark matter consists of and why it has not yet been possible to directly observe a CP violation for the strong interaction.

The “MADMAX” project is the MPP’s commitment to axion research. Axions are so far only a theoretical prediction and are difficult to detect: on the one hand,...

Im Focus: Molecules change shape when wet

Broadband rotational spectroscopy unravels structural reshaping of isolated molecules in the gas phase to accommodate water

In two recent publications in the Journal of Chemical Physics and in the Journal of Physical Chemistry Letters, researchers around Melanie Schnell from the Max...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

ICTM Conference 2017: Production technology for turbomachine manufacturing of the future

16.11.2016 | Event News

Innovation Day Laser Technology – Laser Additive Manufacturing

01.11.2016 | Event News

#IC2S2: When Social Science meets Computer Science - GESIS will host the IC2S2 conference 2017

14.10.2016 | Event News

 
Latest News

High-precision magnetic field sensing

05.12.2016 | Power and Electrical Engineering

Construction of practical quantum computers radically simplified

05.12.2016 | Information Technology

NASA's AIM observes early noctilucent ice clouds over Antarctica

05.12.2016 | Earth Sciences

VideoLinks
B2B-VideoLinks
More VideoLinks >>>