Navigation Links
Protein Targets for Carcinogenesis

Misfolded and disused proteins are eliminated by a cellular shredder called the proteasome. The cell labels the proteins it wants to dispose with Ubiquitin (Ub) in order to avoid the unwanted degradation of still needed proteins. Malfunctions in the ubiquitin-proteasome system can be fatal for the organism.

In particular cancer and immunological disorders but also developmental defects are the consequences. The knowledge about the ubiquitination reaction as well as the effect of ubiquitination on diverse cellular functions has already led to the development of highly promising drugs like Bortezomib and Herceptin.

The molecular mechanism of Ub conjugation and its biological meaning has been discovered by Avram Hershko, Aaron Ciechanover and Irwin Rose who have been awarded the noble price for their work in 2004. In the current issue of Molecular Cell Prof. Ivan Dikic and his team from the institute of biochemistry II at the University of Frankfurt now describe a novel Ub conjugation reaction that might allow a more efficient manipulation of key proteins in the treatment of cancer and other diseases.

Our current view on protein ubiquitination as it is found in the textbooks has to be revised, explains Prof. Mller-Esterl, director of the institute of biochemistry and vice president of the Johann-Wolfgang-Goethe University.

Virtually every process within an eukaryotic cell is directly or indirectly controlled by ubiquitin, says Dikic. This includes fundamental cellular programs such as protein degradation, DNA replication, signal transduction or protein trafficking.

Up to now it was believed that the cooperation of three enzymes is needed to attach Ub to another protein: E1, E2 and E3. E1 activates Ub and transfers it to E2, which in turn cooperates with an so-called Ub ligase (E3) that couples Ub to a specific target protein. However, Dikic and colleagues discovered that certain proteins can be ubiqui tinated independently of E3 ligases which caused a stir among experts.

A prerequisite for the E3-independent reaction is the presence of a Ub-binding domain (UBD) in the protein that is able to recognize Ub. This type of protein is of utmost importance for the cell because it can distinguish between ubiquitinated and non-ubiquitinated proteins, explains Dr. Daniela Hoeller, the responsible scientist. UBD-proteins are the key to the effects of Ub both in normal and malignant cells.

Dikic and his coworkers demonstrated that proteins equipped with an UBD can ubiquitinate themselves by directly recruiting Ub-loaded E2 enzymes thus making E3 ligases dispensible. In their previous work Hoeller and Dikic showed that the ubiquitination of UBD proteins does not lead to their degradation but rather causes their functional inactivation.

In other words they become unable to recognize and control ubiquitinated proteins. If needed the cell can re-activated them by cleaving the attached Ub. In this way the cell can quickly and dynamically react on external signals.

The discovery provides the basis for novel therapeutic approaches that are more specific than drugs like Bortezomib. For an effective therapeutic use there is still a long way to go, explains Mller-Esterl, who needs to update his biochemistry textbook now.


'"/>




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:1/23/2017)... ... January 23, 2017 , ... DMG Productions is proud to ... Jr., scheduled to broadcast Saturday, January 28, 2017 at 5:00pmEST. , This segment ... to address the limitations of fatigue monitoring technologies within the mining industry. Today ...
(Date:1/23/2017)... ... January 23, 2017 , ... ... taught by healthcare management and evaluation leaders with decades of experience who remain ... in the United States healthcare system, there is a renewed demand for versatile, ...
(Date:1/23/2017)... Indiana (PRWEB) , ... January 23, 2017 , ... ... Center for Assisted Living (IHCA/INCAL), will serve as a healthcare industry expert at ... 23. The panel discussion, moderated by Inside Indiana Business host Gerry Dick, will ...
(Date:1/23/2017)... ... 23, 2017 , ... Steviva Ingredients, makers of all-natural sweeteners ... National Organic Program (NOP) for its Portland SQF Level 2 manufacturing facility. ... handling systems to complement our current rigorous food-safety management systems,” said Yishu Hou, ...
(Date:1/23/2017)... ... January 23, 2017 , ... ... partnership with the American Society of Anesthesiologists® (ASA®), the Foundation for Anesthesia ... Academy of Orthopaedic Surgeons (AAOS) and the Cigna Foundation, encourages proposals supporting ...
Breaking Medicine News(10 mins):
(Date:1/21/2017)... Jan. 20, 2017 ResMed (NYSE: RMD ), ... Winter Haven, Florida ) today announced they have agreed ... and 3B will be permitted to sell their existing products in ... one-time settlement payment to 3B to close the Florida ... include an admission of liability or wrongdoing by any party. ...
(Date:1/21/2017)... Jan. 20, 2017  Faruqi & Faruqi, LLP, a leading ... or the "Company") (NASDAQ: KMPH ) of the ... certain officers and directors and underwriters of the Company,s April ... role of lead plaintiff. The lawsuit has been ... for Johnson County on behalf of ...
(Date:1/20/2017)... Research and Markets has announced the addition of the ... to their offering. ... This research service on the global pharmaceutical stability testing market ... of the key participants in the market. The ... 2020. The market is expected to grow at a CAGR of ...
Breaking Medicine Technology: