Featured Research

from universities, journals, and other organizations

Nuclear receptors battle it out during metamorphosis in new fruit fly model

Date:
October 12, 2011
Source:
Thomas Jefferson University
Summary:
Growing up just got more complicated. Biochemistry researchers have shown for the first time that the receptor for a major insect molting hormone doesn't activate and repress genes as once thought. In fact, it only activates genes, and it is out-competed by a heme-binding receptor to repress the same genes during the larval to pupal transition in the fruit fly.

Growing up just got more complicated. Thomas Jefferson University biochemistry researchers have shown for the first time that the receptor for a major insect molting hormone doesn't activate and repress genes as once thought. In fact, it only activates genes, and it is out-competed by a heme-binding receptor to repress the same genes during the larval to pupal transition in the fruit fly.

For the last 20 years, the nuclear receptor known as EcR/Usp was thought to solely control gene transcription depending on the presence or absence of the hormone ecdysone, respectively. But it appears, researchers found, that E75A, a heme-binding receptor that represses genes, replaces EcR/Usp during metamorphosis when ecdysone is absent.

The findings, which could shed light on new ways to better understand and treat hormone-dependent diseases, such as cancer, were published in the online October 6 issue of Molecular Cell.

"This is the first time we've shown that a steroid hormone receptor and heme-binding nuclear receptor are even interacting with each other," said Danika M. Johnston, Ph.D. "We didn't really think the two were competing against each other to bind to the same sequence of DNA and regulate the same genes."

More specifically, in the absence of ecdysone, both ecdysone receptor subunits localize to the cytoplasm, and the heme-binding nuclear receptor E75A replaces EcR/Usp at common target sequences in several genes. During the larval-pupal transition, a switch from gene activation by EcR/Usp to gene repression by E75A is triggered by a decrease in ecdysone concentration and by direct repression of the EcR gene by E75A.

An important nuance of this system is that the heme-binder E75A is sensitive to the amount of nitric oxide in the cell, and it cannot completely fulfill its repressive potential at high levels of this important molecule. Thus, the uncovered system uses changing amounts of two ligands, a steroid hormone and a gas, to regulate transcription during development.

"These were quite unexpected findings, given the longstanding thoughts of this process," said Dr. Johnston, "but we just didn't have the tools in the past to figure out what was going on mechanistically. We're painting a clearer picture now."

Knowing how nuclear receptors regulate gene expression in animal models can provide useful information in the development of drugs. Today, the molecular targets of roughly 13 percent of U.S. Food and Drug Administration approved drugs are nuclear receptors.

"It's very possible that similar situations exist in the mammalian system. That could ultimately lead to different treatments that regulate hormone levels in hormone-dependent diseases, such as cancer," said Dr. Johnston.

This investigation took place in the lab of co-author Alexander M. Mazo, Ph.D., a professor of the Department of Biochemistry and Molecular Biology at Jefferson.


Story Source:

The above story is based on materials provided by Thomas Jefferson University. Note: Materials may be edited for content and length.


Journal Reference:

  1. Danika M. Johnston, Yurii Sedkov, Svetlana Petruk, Kristen M. Riley, Miki Fujioka, James B. Jaynes, Alexander Mazo. Ecdysone- and NO-Mediated Gene Regulation by Competing EcR/Usp and E75A Nuclear Receptors during Drosophila Development. Molecular Cell, Volume 44, Issue 1, 51-61, 7 October 2011 DOI: 10.1016/j.molcel.2011.07.033

Cite This Page:

Thomas Jefferson University. "Nuclear receptors battle it out during metamorphosis in new fruit fly model." ScienceDaily. ScienceDaily, 12 October 2011. <www.sciencedaily.com/releases/2011/10/111006125414.htm>.
Thomas Jefferson University. (2011, October 12). Nuclear receptors battle it out during metamorphosis in new fruit fly model. ScienceDaily. Retrieved July 31, 2014 from www.sciencedaily.com/releases/2011/10/111006125414.htm
Thomas Jefferson University. "Nuclear receptors battle it out during metamorphosis in new fruit fly model." ScienceDaily. www.sciencedaily.com/releases/2011/10/111006125414.htm (accessed July 31, 2014).

Share This




More Plants & Animals News

Thursday, July 31, 2014

Featured Research

from universities, journals, and other organizations


Featured Videos

from AP, Reuters, AFP, and other news services

Visitors Feel Part of the Pack at Wolf Preserve

Visitors Feel Part of the Pack at Wolf Preserve

AP (July 31, 2014) — Seacrest Wolf Preserve on the northern Florida panhandle allows more than 10,000 visitors each year to get up close and personal with Arctic and British Columbian Wolves. (July 31) Video provided by AP
Powered by NewsLook.com
Florida Panther Rebound Upsets Ranchers

Florida Panther Rebound Upsets Ranchers

AP (July 31, 2014) — With Florida's panther population rebounding, some ranchers complain the protected predators are once again killing their calves. (July 31) Video provided by AP
Powered by NewsLook.com
Dangerous Bacteria Kills One in Florida

Dangerous Bacteria Kills One in Florida

AP (July 31, 2014) — Sarasota County, Florida health officials have issued a warning against eating raw oysters and exposing open wounds to coastal and inland waters after a dangerous bacteria killed one person and made another sick. (July 31) Video provided by AP
Powered by NewsLook.com
Raw: Thousands Flocking to German Crop Circle

Raw: Thousands Flocking to German Crop Circle

AP (July 30, 2014) — Thousands of people are trekking to a Bavarian farmer's field to check out a mysterious set of crop circles. (July 30) Video provided by AP
Powered by NewsLook.com

Search ScienceDaily

Number of stories in archives: 140,361

Find with keyword(s):
 
Enter a keyword or phrase to search ScienceDaily for related topics and research stories.

Save/Print:
Share:  

Breaking News:
from the past week

In Other News

... from NewsDaily.com

Science News

Health News

    Environment News

    Technology News



      Save/Print:
      Share:  

      Free Subscriptions


      Get the latest science news with ScienceDaily's free email newsletters, updated daily and weekly. Or view hourly updated newsfeeds in your RSS reader:

      Get Social & Mobile


      Keep up to date with the latest news from ScienceDaily via social networks and mobile apps:

      Have Feedback?


      Tell us what you think of ScienceDaily -- we welcome both positive and negative comments. Have any problems using the site? Questions?
      Mobile iPhone Android Web
      Follow Facebook Twitter Google+
      Subscribe RSS Feeds Email Newsletters
      Latest Headlines Health & Medicine Mind & Brain Space & Time Matter & Energy Computers & Math Plants & Animals Earth & Climate Fossils & Ruins