Navigation Links
An AIDS-related virus tricks cells to become tumors, new Penn study finds

Researchers at the University of Pennsylvania School of Medicine have discovered how the Kaposi's sarcoma-associated herpesvirus (KSHV) subverts a normal cell process in order to promote tumor growth. The finding, published in the most recent issue of PLoS Pathogens, offers new potential strategies for treating Kaposi's sarcoma and other cancers associated with viruses.

KSHV is an opportunistic pathogen that rarely affects individuals with normal immune systems. However, HIV/AIDS patients and those who are immune suppressed such as organ transplant patients are at high risk for developing Kaposi's sarcoma and another cancer called primary effusion lymphoma.

The study describes how a KSHV-encoded protein, called latency-associated nuclear antigen, or LANA, tricks the cell into destroying two major suppressors of tumor growth called von Hippel Lindau (VHL) and p53. "In addition, we have shown that when LANA expression was blocked, the tumor suppressors again become stable suggesting a direct role of the viral protein in regulation of these major cell proteins," says lead author Erle Robertson, PhD, Professor of Microbiology and the Director of Tumor Virology at Penn's Abramson Cancer Center.

Marked for Disposal The trick is played out in a cell process called ubiquitylation. This refers to a pathway in all cells whereby a protein aptly named ubiquitin binds to cellular proteins and marks them for degradation. This process can be likened to putting out the garbage for disposal.

Ubiquitylation and degradation involve a complex set of proteins in addition to ubiquitin. "We found that the viral LANA has an amino acid motif that mimics non-viral cell proteins usually involved in the ubiquitylation process," says Robertson. This motif, or stretch of amino acids, normally enables LANA to bind to tumor suppressors p53 or VHL, thus bringing them into the active ubiquitylation complex. Once in the complex, the tumor suppressors are target ed for degradation.

Tumor suppressors, as their name implies, prevent or limit the growth of tumors in numerous ways. One way the tumor suppressors p53 and VHL work is to mark a key protein that controls the blood supply in a tumor mass. Once marked, this protein called hypoxia-induced factor 1a (HIF-1a) is degraded through ubiquitylation before it can start the process of activating genes responsible for inducing growth of more blood vessels to supply the tumor with oxygen. However, in a KSHV-infected cell, p53 and VHL themselves would be targeted for degradation and HIF-1a would then be free to activate genes involved in growth of blood vessels to increase the blood supply to the tumor.

"Use of such proteosome inhibitors as Bortezomib as cancer therapeutic agents has been ongoing for the last four to five years and this study provides crucial step in understanding the mechanism for anti-tumorigenic activity against KSHV-associated human cancers," concludes Robertson. "Additionally, we can now use compounds known to inhibit proteosome activity to determine their effectiveness in inhibiting the Kaposi's viral-induced degradation of these two major tumor suppressors." This, he says, is important in finding or designing drugs that can be specifically used against KSHV, and potentially, other virus-associated cancers.

Source:University of Pennsylvania School of Medicine

Related biology news :

1. Combination therapy improves AIDS-related lymphoma outcome
2. AIDS-related cognitive impairment exists in two separate forms
3. Association of herpesvirus with lung disorder questioned
4. Topical treatment shown to inhibit HIV and herpes simplex virus infection
5. Elusive HIV shape change revealed; Key clue to how virus infects cells
6. Newly discovered virus linked to childhood lung disorders and Kawasaki disease
7. Live Recombinant Adenovirus Vaccine Technique Explored
8. Marburg virus disease in Angola - update
9. Studies reveal methods viruses use to sidestep immune system
10. Norovirus, AIDS vaccine and Hepatitis Virus
11. Epstein-Barr virus protein crucial to its role in blood cancers

Post Your Comments:

(Date:11/17/2015)... , Nov. 17, 2015 Pressure BioSciences, Inc. ... the development and sale of broadly enabling, pressure cycling ... sciences industry, today announced it has received gross proceeds ... million Private Placement (the "Offering"), increasing the total amount ... or more additional closings are expected in the near ...
(Date:11/12/2015)... golden retriever that stayed healthy despite having the gene ... new lead for treating this muscle-wasting disorder, report scientists ... and Harvard and the University of São Paolo in ... pinpoints a protective gene that boosts muscle regeneration, ... Children,s lab of Lou Kunkel , PhD, is ...
(Date:11/12/2015)... Nov. 11, 2015   Growing need for ... tools has been paving the way for use ... of discrete analytes in clinical, agricultural, environmental, food ... predominantly used in medical applications, however, their adoption ... due to continuous emphasis on improving product quality ...
Breaking Biology News(10 mins):
(Date:11/25/2015)... ... 25, 2015 , ... Jessica Richman and Zachary Apte, founders ... initial angel funding process. Now, they are paying it forward to other microbiome ... investments in the microbiome space. In this, they join other successful entrepreneurs-turned-angels ...
(Date:11/24/2015)... , Nov. 24, 2015 Cepheid (NASDAQ: ... speaking at the following conference, and invited investors to ... NY      Tuesday, December 1, 2015 at 11.00 ... NY      Tuesday, December 1, 2015 at 11.00 ... Conference, New York, NY      Tuesday, ...
(Date:11/24/2015)... (PRWEB) , ... November 24, 2015 , ... ... maintain healthy metabolism. But unless it is bound to proteins, copper is also ... Health (NIH), researchers at Worcester Polytechnic Institute (WPI) will conduct a systematic study ...
(Date:11/24/2015)... -- Clintrax Global, Inc., a worldwide provider of clinical research services headquartered ... the company has set a new quarterly earnings record in Q3 ... posted for Q3 of 2014 to Q3 of 2015.   ... , with the establishment of an Asia-Pacific ... United Kingdom and Mexico , with ...
Breaking Biology Technology: