The protein, named Kibra, is linked to a relay of chemical signals responsible for shaping and sizing tissue growth by coordinating control of cell proliferation and death, according to research published Feb. 16 in Developmental Cell by teams at Johns Hopkins and Florida State University.
In a series of experiments, the scientists manipulated Kibra’s role in a signaling network called the Hippo pathway, which consists of several proteins working together as a braking system. Counterparts of the components in the Hippo pathway in flies are found in most animals, suggesting that this pathway may act as a “global regulator” of organ size control, according to Duojia Pan, Ph.D., a professor of molecular biology and genetics at Johns Hopkins University School of Medicine and an investigator of the Howard Hughes Medical Institute.
“People have always been curious about what makes a hippopotamus grow so much bigger than a mouse,” says Pan, “as well as how our two hands, which develop independently, get to very similar sizes. Our studies show that Kibra regulates Hippo, which keeps organs characteristically sized, preventing my heart or your liver from becoming as hefty as those befitting a large African amphibious mammal,” he adds, referring to the signaling pathway’s name.
Pan's team identified the gene they named Hippo in 2003, showing that an abnormal copy of it led to an unusually large eye in a developing fruit fly. Two years later, the team established that Hippo lies in the middle of a signaling cascade: Its “stop growing” message is relayed along a molecular pathway of biochemically linked proteins, which limits the expression of genes that otherwise promote cell division and cell survival. In 2007, they showed that by manipulating the pathway in a mouse liver, the organ grew to five times its normal size and became cancerous.
The new experiments, Pan says, moved the investigation “slowly and methodically upstream” to find Hippo’s trigger, where, he believes, “the key to size-control lies.” The Hippo-Kibra link could be a key to understanding and treating cancer, Pan adds, because cancer is literally a disease of uncontrolled growth.
The Johns Hopkins and Florida State teams discovered Kibra by studying ovarian cells from adult flies and by using a gene-controlling technique called RNA interference (RNAi) to systematically turn off each of the approximately 14,000 genes in the fly genome, one at a time, in cultured fly cells. They then analyzed the function of Kibra in the developing fly larvae. Each of the specialized discs that develop into a fly’s eyes starts out with approximately 30 to 40 cells and then grows by about a thousand-fold in the larval stage before stopping, making larvae the ideal place to catch the right-sizing process in action, Pan says. These studies told them that the Hippo pathway was not active in the absence Kibra.
Further studies on human cells measured the activity of the Hippo pathway while manipulating human Kibra and showed that like its fruit fly counterpart, human Kibra acts as a tumor suppressor protein that regulates Hippo signaling.
“The discovery of Kibra moves us an important step closer to identifying the initial signal that triggers Hippo’s activation,” Pan says. “We’re making progress along the Hippo pathway, heading toward the cell surface, and believe we will find that elusive signal en route.”
The name Kibra, a shortened combination of the words kidney and brain, is based on earlier evidence that Kibra is prominently expressed in those two organs. Kibra’s role in memory performance in humans has already garnered interest.
Authors of the paper, in addition to Pan, are Jianzhong Yu, Stephen Klusza and Wu-Min Deng of Florida State University; and Yonggang Zheng and Jixin Dong of Johns Hopkins.
This research was supported by grants from the National Institutes of Health.On the Web:
Maryalice Yakutchik | Newswise Science News
Link Discovered between Immune System, Brain Structure and Memory
26.04.2017 | Universität Basel
Researchers develop eco-friendly, 4-in-1 catalyst
25.04.2017 | Brown University
More and more automobile companies are focusing on body parts made of carbon fiber reinforced plastics (CFRP). However, manufacturing and repair costs must be further reduced in order to make CFRP more economical in use. Together with the Volkswagen AG and five other partners in the project HolQueSt 3D, the Laser Zentrum Hannover e.V. (LZH) has developed laser processes for the automatic trimming, drilling and repair of three-dimensional components.
Automated manufacturing processes are the basis for ultimately establishing the series production of CFRP components. In the project HolQueSt 3D, the LZH has...
Reflecting the structure of composites found in nature and the ancient world, researchers at the University of Illinois at Urbana-Champaign have synthesized thin carbon nanotube (CNT) textiles that exhibit both high electrical conductivity and a level of toughness that is about fifty times higher than copper films, currently used in electronics.
"The structural robustness of thin metal films has significant importance for the reliable operation of smart skin and flexible electronics including...
The nearby, giant radio galaxy M87 hosts a supermassive black hole (BH) and is well-known for its bright jet dominating the spectrum over ten orders of magnitude in frequency. Due to its proximity, jet prominence, and the large black hole mass, M87 is the best laboratory for investigating the formation, acceleration, and collimation of relativistic jets. A research team led by Silke Britzen from the Max Planck Institute for Radio Astronomy in Bonn, Germany, has found strong indication for turbulent processes connecting the accretion disk and the jet of that galaxy providing insights into the longstanding problem of the origin of astrophysical jets.
Supermassive black holes form some of the most enigmatic phenomena in astrophysics. Their enormous energy output is supposed to be generated by the...
The probability to find a certain number of photons inside a laser pulse usually corresponds to a classical distribution of independent events, the so-called...
Microprocessors based on atomically thin materials hold the promise of the evolution of traditional processors as well as new applications in the field of flexible electronics. Now, a TU Wien research team led by Thomas Müller has made a breakthrough in this field as part of an ongoing research project.
Two-dimensional materials, or 2D materials for short, are extremely versatile, although – or often more precisely because – they are made up of just one or a...
20.04.2017 | Event News
18.04.2017 | Event News
03.04.2017 | Event News
27.04.2017 | Health and Medicine
27.04.2017 | Information Technology
26.04.2017 | Materials Sciences