Scientists gain new insights into Taspase1 function

July 10, 2012

Scientists at the University Medical Center of Johannes Gutenberg University Mainz in Germany identified a novel strategy to target the oncologically relevant protein-cleaving enzyme Taspase1. Taspase1 levels are not only elevated in cancer cells of patients with head and neck tumors and other solid malignancies but the enzyme is also critical for the development of leukemias. Central to this concept is the approach to inhibit the enzyme's activity by 'gluing together' individual Taspase1 molecules. The results of a study undertaken by Professor Dr. Roland Stauber of the ENT Department at the Mainz University Medical Center were recently published in The FASEB Journal.

Protein-cleaving enzymes, so-called , are not only significantly involved in in the healthy body, such as blood clotting, but also play critical roles in illnesses, such as cancer, Alzheimer's, and . Several have already been developed and are being used against some of these 'disease-causing' enzymes with varying success in the clinics. However, one representative of this in particular – the protease Taspase1 – is troubling researchers worldwide." We currently do not have any drug that can inhibit Taspase1. And we still do not understand in sufficient detail how this enzyme really works," says Stauber.

Almost ten years ago, the team found enhanced levels of Taspase1 in the of patients with head and neck tumors. At that time, the function of the protease in tumor cells and its relevance for disease was still unknown. Recent findings support the oncological importance of Taspase1 for solid malignancies and leukemias. Taspase1 appears to override control mechanisms in healthy cells by cleaving various other proteins, thereby significantly promoting cancer development. As a result of extensive research supported by funding provided by the Head and Neck Tumor Research Foundation [Stiftung Tumorforschung], the German Cancer Aid, the Thyssen Foundation, and Johannes Gutenberg University Mainz, the researchers have now gained new insights into the enzyme's molecular functions. "Previously, it was assumed that two Taspase1 enzymes had to come together in order to be active and cleave other cellular proteins," explains Stauber. "Our latest results not only demonstrate that one Taspase1 molecule is sufficient for this, but also that we can even block the tumor-promoting properties of the enzyme by 'gluing' two Taspase1 molecules together."

Hence, the Mainz-based researchers identified a completely novel approach to developing drugs that may be used to inhibit Taspase1. "We are now searching for chemical substances that could function as molecular Taspase1 'adhesives'," adds Stauber. As part of the so-called Chemical BioMedicine Initiative, the scientists are betting on nature's vast chemical repertoire. "Natural products from fungi and marine sponges are a highly privileged source for potential new drugs. Evolution already pre-checked the biological qualities of such chemical substances in living organisms. Thus, we have a good chance of finding the right chemical decoys," predicts Stauber. "The robotic platform at the Mainz Screening Center combined with our Taspase1 assays will play a leading role in this search for the 'needle in the haystack'."

Explore further: New immune defence enzyme discovered

Related Stories

New immune defence enzyme discovered

April 3, 2012
(Medical Xpress) -- Neutrophil granulocytes comprise important defences for the immune system. When pathogenic bacteria penetrate the body, they are the first on the scene to mobilise other immune cells via signal molecules, ...

Researchers discover protein that could help prevent the spread of cancer

May 4, 2011
A protein capable of halting the spread of breast cancer cells could lead to a therapy for preventing or limiting the spread of the disease.

Recommended for you

Study prompts new ideas on cancers' origins

December 16, 2017
Rapidly dividing, yet aberrant stem cells are a major source of cancer. But a new study suggests that mature cells also play a key role in initiating cancer—a finding that could upend the way scientists think about the ...

What does hair loss have to teach us about cancer metastasis?

December 15, 2017
Understanding how cancer cells are able to metastasize—migrate from the primary tumor to distant sites in the body—and developing therapies to inhibit this process are the focus of many laboratories around the country. ...

Cancer immunotherapy may work better in patients with specific genes

December 15, 2017
Cancer cells arise when DNA is mutated, and these cells should be recognized as "foreign" by the immune system. However, cancer cells have found ways to evade detection by the immune system.

Scientists pinpoint gene to blame for poorer survival rate in early-onset breast cancer patients

December 15, 2017
A new study led by scientists at the University of Southampton has found that inherited variation in a particular gene may be to blame for the lower survival rate of patients diagnosed with early-onset breast cancer.

Scientists unlock structure of mTOR, a key cancer cell signaling protein

December 14, 2017
Researchers in the Sloan Kettering Institute have solved the structure of an important signaling molecule in cancer cells. They used a new technology called cryo-EM to visualize the structure in three dimensions. The detailed ...

'Bet hedging' explains the efficacy of many combination cancer therapies

December 14, 2017
The efficacy of many FDA-approved cancer drug combinations is not due to synergistic interactions between drugs, but rather to a form of "bet hedging," according to a new study published by Harvard Medical School researchers ...

0 comments

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.