Navigation Links
"Tribbles" Protein Implicated in 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/EBP?, 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/EBP? 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 sort s, activating 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/EBP?.

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-Newswis
SRM
'"/>




Related medicine news :

1. Lean Protein Could Be Key to Obesity Drugs
2. Evidence Links Protein Damage to Neurodegenerative diseases like Parkinsons and Alzheimers
3. Unravelling the secrets of ‘Huntingtin’ Protein - towards the treatment of ‘Huntingtons’ Disase
4. Unravelling the secrets of ‘Huntingtin’ Protein - towards the treatment of Huntingtins’ Disese
5. Protein in urine foresees heart disease
6. Levels Of Blood Proteins May Help Heart Disease Care
7. Protein signals need for heart surgery
8. Protein and fat improve memory
9. Clotting Protein plays a role in nerve repair
10. High Levels of Protein Linked to Brain Shrinkage
11. Protein can change worn muscle fibres
Post Your Comments:
*Name:
*Comment:
*Email:


(Date:10/13/2017)... Ill. (PRWEB) , ... October ... ... Edwardsville School of Pharmacy (SOP) alumni Hannah Randall, PharmD ‘17, and Jennifer ... healthcare professionals on guideline updates for the primary prevention of cardiovascular diseases ...
(Date:10/13/2017)... ... October 13, 2017 , ... Many families have long-term insurance that covers ... companies have a waiver for care if the client has a cognitive impairment diagnosis. ... pays for care, is often waived, so the benefits from their insurance start immediately,” ...
(Date:10/13/2017)... ... October 13, 2017 , ... Global Healthcare Management’s 4th ... Park in Milford, NJ. This free event, sponsored by Global Healthcare Management’s CEO, ... The fun run is geared towards children of all ages; it is a non-competitive, ...
(Date:10/13/2017)... ... October 13, 2017 , ... Coveros, ... Development, has been awarded a contract by the Center for Medicare and Medicaid ... to accelerate the enterprise use of Agile methodologies in a consistent and high ...
(Date:10/12/2017)... ... 2017 , ... First Healthcare Compliance (FHC), an industry leader ... range of technology and learning solutions at the 68th Annual American Healthcare Association ... held October 14–18, 2017 at the Mandalay Bay Resort in Las Vegas, Nevada. ...
Breaking Medicine News(10 mins):
(Date:9/25/2017)...  EpiVax, Inc., a leader in the fields ... announced the launch of EpiVax Oncology Inc., a ... cancer vaccines. EpiVax has provided $500,000 in seed ... technologies to the new precision immunotherapy venture. Gad ... as Chief Executive Officer. Gad brings over 25 ...
(Date:9/22/2017)... , Sept. 22, 2017  As the latest Obamacare ... Bill Cassidy (R-LA) and Lindsey Graham ... that the medical device industry is in an odd ... tax, the 2.3% excise tax on medical device sales ... also want covered patients, increased visits and hospital customers ...
(Date:9/19/2017)... 2017 HistoSonics, Inc., a venture-backed medical device company developing a non-invasive, robotically assisted, ... three leadership team developments today:   ... ... Tom Tefft ... Veteran medical device executive Josh Stopek , PhD, who has ...
Breaking Medicine Technology: