Navigation Links
'Tribbles' protein implicated in common and aggressive form of leukemia

Researchers at the University of Pennsylvania School of Medicine have identified a new protein associated with acute myelogenous leukemia (AML). Several lines of evidence point to a protein called Tribbles, named after the furry creatures that took over the starship Enterprise in the original Star Trek series. Tribbles was first described in fruit flies.

"Tribbles had never been directly linked to human malignancy," says senior author Warren S. Pear, MD, PhD, Associate Professor of Pathology and Laboratory Medicine. "This is a new protein to human cancer and has a specific and overwhelming effect when expressed in hematopoietic stem cells, the cell type that gives rise to all elements of the blood."

Three lines of evidence implicate Tribbles in AML. First, all mice engineered to express Tribbles-2 (Trib-2) in hematopoietic stem cells developed AML. They also found that Trib-2 inhibited C/EBPá, another protein that is frequently mutated in AML patients. Additionally, expression of the Tribbles protein was elevated in blood samples from AML patients, further suggesting that it contributes to AML. Overall, the findings suggest that Tribbles induces AML by inactivating the C/EBPá protein. The results were published in this week's issue of Cancer Cell.

AML is a malignancy that arises in white blood cells and develops when there is a defect in immature immune cells in the bone marrow. In AML, the uncontrolled, exaggerated growth and accumulation of white blood cells leads to anemia and a deficiency of normal white cells in the blood. AML is the most common type of leukemia in adults, with an estimated 10,100 new cases reported each year.

Pear, also a researcher in the Abramson Family Cancer Research Institute at Penn; first author and postdoctoral fellow Karen Keeshan, PhD; and colleagues found Tribbles by chance when looking for the molecular partners of another protein called Notch. Notch is a molecular switch of sorts, activati ng gene transcription in the nucleus of many types of cells, and depending on the biochemical context, turns certain pathways on and others off.

Pear and colleagues knew from fruit fly studies that the Tribbles protein was linked to cell growth and cell-fate determination and is closely related to the Tribbles gene in mammals. In fact, Tribbles is so named because, when mutated in flies, it causes cells to proliferate uncontrollably.

Accumulating evidence from several groups shows that Tribbles functions as a scaffold to bring together a complex that mediates protein degradation. Protein degradation is required for normal cellular function; however, data from the Pear lab suggests that mistakes in the expression of the Tribbles gene may lead to degradation of proteins that hold cancer in check, such as tumor suppressors. "One of our current challenges is to determine what other proteins Tribbles degrades to cause leukemia," says Pear.

The findings in mice were also validated in a large database of human cancer patients. In a survey of gene expression in AML patients, high Tribbles expression was found in a subset of patients who had been previously characterized by defects in C/EBPá.

According to Keeshan, "C/EBPa defects have also been identified in lung cancer and other tumors, suggesting the possibility that Trib2 dysregulation may be identified in other tumors. Furthermore, linking Trib2 to human cancer adds further support to the notion that targeting the protein degradation machinery will be a useful strategy in treating malignancy."

Source:University of Pennsylvania School of Medicine

Related biology news :

1. New, automated tool successfully classifies and relates proteins in unprecedented way
2. New binding target for oncogenic viral protein
3. Controversial drug shown to act on brain protein to cut alcohol use
4. Timing is everything: First step in protein building revealed
5. UWs Rosetta software to unlock secrets of many human proteins
6. Researchers find how protein allows insects to detect and respond to pheromones
7. Signaling protein builds bigger, better bones in mice
8. Ancient olfaction protein is shared by many bugs, offering new pest control target
9. Automatic extraction of gene/protein biological functions from biomedical text
10. Discovery of key proteins shape could lead to improved bacterial pneumonia vaccine
11. Scientists develop new color-coded test for protein folding

Post Your Comments:

(Date:11/17/2015)... -- Paris , qui s,est ... Paris , qui s,est tenu du 17 ... de l,innovation biométrique, a inventé le premier scanner couplé, ... la même surface de balayage. Jusqu,ici, deux scanners étaient ... empreintes digitales. Désormais, un seul scanner est en mesure ...
(Date:11/12/2015)... , Nov. 12, 2015  A golden retriever ... Duchenne muscular dystrophy (DMD) has provided a new lead ... Children,s Hospital, the Broad Institute of MIT and Harvard ... Brazil . Cell, pinpoints ... dogs "escape" the disease,s effects. The Boston Children,s lab ...
(Date:11/10/2015)... , Nov. 10, 2015  In ... on the basis of product, type, application, ... included in this report are consumables, services, ... report are safety biomarkers, efficacy biomarkers, and ... this report are diagnostics development, drug discovery ...
Breaking Biology News(10 mins):
(Date:11/30/2015)... DIEGO , Nov. 30, 2015  HUYA Bioscience ... China,s pharmaceutical innovations, today announced it ... Drug Development Fund (KDDF) to foster collaboration between KDDF ... development and commercialization of healthcare products for the global ... as an important source of new innovative preclinical and ...
(Date:11/30/2015)... CA (PRWEB) , ... November ... ... Intelligence Company, today announced tighter software integration with MarkLogic, the Enterprise NoSQL ... organizations maximize information to drive change. , Smartlogic’s Content Intelligence capabilities provide ...
(Date:11/27/2015)... November 27, 2015 ... popularity of companion diagnostics is one of ... market with pharmaceutical companies and diagnostic manufacturers ... tests. . --> ... report on global cancer biomarkers market spread ...
(Date:11/25/2015)... 2 nouvelles études permettent d ... différences entre les souches bactériennes retrouvées dans la plaque ... humains . Ces recherches  ouvrent une nouvelle ... charge efficace de l,un des problèmes de santé ... .    --> 2 nouvelles études permettent d ...
Breaking Biology Technology: