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:
*Name:
*Comment:
*Email:


(Date:4/17/2017)... April 17, 2017 NXT-ID, Inc. (NASDAQ: ... the filing of its 2016 Annual Report on Form 10-K on ... ... is available in the Investor Relations section of the Company,s website ... SEC,s website at http://www.sec.gov . 2016 Year Highlights: ...
(Date:4/11/2017)... No two people are believed to ... York University Tandon School of Engineering and Michigan ... partial similarities between prints are common enough that ... and other electronic devices can be more vulnerable ... in the fact that fingerprint-based authentication systems feature ...
(Date:4/5/2017)... LONDON , April 4, 2017 KEY ... is anticipated to expand at a CAGR of 25.76% ... neurodegenerative diseases is the primary factor for the growth ... full report: https://www.reportbuyer.com/product/4807905/ MARKET INSIGHTS The ... of product, technology, application, and geography. The stem cell ...
Breaking Biology News(10 mins):
(Date:8/15/2017)... ... August 15, 2017 , ... Kapstone Medical is ... of successes helping medical technology companies and inventors develop and safeguard their latest innovations. ... national engineering firm with a portfolio of clients in the United States and around ...
(Date:8/15/2017)... ... , ... The Conference Forum and The Trout Group ... of upcoming panels and events. The partnership culminates with the 4th Annual IO360° ... York City. , “With our experience in producing the Immuno-Oncology 360° NYC event and ...
(Date:8/14/2017)... ... August 14, 2017 , ... The Conference Forum has confirmed ... take place on September 6, 2017 at the Marriott Copley Place in Boston, MA. ... Medicine, Informatics, and Regulatory Strategy, Pfizer Innovative Research Lab, Pfizer, who leads 19 industry ...
(Date:8/10/2017)... ... August 09, 2017 , ... As ... industry reach its ideal customers with the right message. Their effective, cutting-edge inbound ... Midwest company, we realize how crucial the agriculture industry is,” said David Phelps, ...
Breaking Biology Technology: