Navigation Links
Static killers?
Date:9/6/2013

Since its discovery in the early 1990s, the protein STAT1 (Signal Transducer and Activator of Transcription 1) has been found to be central in passing signals across immune cells, ensuring that our bodies react quickly and appropriately to threats from viruses or other pathogens. Animals without STAT1 are also prone to develop cancer, suggesting that STAT1 is somehow involved in protection against malignant cells. The STAT1 protein is known to be phosphorylated on at least two positions: phosphorylation of a particular tyrosine (tyr-701) is required for the protein to enter the cell nucleus (where it exerts its effects), while subsequent phosphorylation of a serine residue alters the way it interacts with other proteins, thereby affecting its function.

Natural Killer (NK) cells are among the first cells to respond to infections by viruses or to attack malignant cells when tumours develop. When they detect cells to be targeted, they produce a number of proteins, such as granzyme B and perforin, that enter infected cells and destroy them from within. Clearly, the lethal activity must be tightly controlled to prevent NK cells from running wild and destroying healthy cells or tissues. How is this done?

Eva Maria Putz and colleagues at the Institute of Pharmacology and Toxicology of the University of Veterinary Medicine, Vienna (Vetmeduni) have now investigated the importance of STAT1 phosphorylation in NK cells. The researchers found that when a particular serine residue (ser-727) in the STAT1 protein is mutated, NK cells produce far higher amounts of granzyme B and perforin and are far more effective at killing a wide range of tumour cells. Mice with the correspondingly mutated Stat1 gene are far less likely to develop melanoma, leukaemia or metastasizing breast cancer. On the other hand, when the same serine residue is phosphorylated, the NK cells are less able to kill infected or cancerous cells.

The Vetmeduni researchers have accumulated a body of evidence to suggest that the cyclin-dependent kinase CDK8 phosphorylates STAT1 on serine 727. Surprisingly, this phosphorylation does not require prior phosphorylation of the activating tyrosine residue, at least in NK cells. Instead, it seems to represent a way in which the lethal activity of the NK cells is kept in check. Putz is keen to note the potential significance of the finding. As she says, "If we can stop CDK8 from inactivating STAT1 in NK cells, we could stimulate tumour surveillance and thus possibly have a new handle on treating cancer, harnessing the body's own weapons against malignant cells."


'/>"/>

Contact: Susanna Kautschitsch
susanna.kautschitsch@vetmeduni.ac.at
43-125-077-1153
University of Veterinary Medicine -- Vienna
Source:Eurekalert

Related biology news :

1. Metastatic pancreatic, primary breast cancer have common growth mechanisms, study suggests
2. How cancer spreads: Metastatic tumor a hybrid of cancer cell and white blood cell
3. Modulating the immune system to combat metastatic cancer
4. LSUHSC research discovers new drug target for metastatic breast cancer
5. Thomas Jefferson University researchers discover new pathways that drive metastatic prostate cancer
6. TGen-US Oncology data guides treatment of metastatic triple-negative breast cancer patients
7. 3dMD Transitions Anatomical Research from 3D-Static to 4D-Movement Surface Imaging
8. Should high-dose interleukin-2 continue to be the treatment of choice for metastatic melanoma?
9. Cancerous tumors deliver pro-metastatic information in secreted vesicles
10. Mechanism found connecting metastatic breast cancer and arthritis
Post Your Comments:
*Name:
*Comment:
*Email:
(Date:6/27/2016)... -- Research and Markets has announced the addition of ... their offering. The report forecasts ... grow at a CAGR of 12.28% during the period 2016-2020. ... market analysis with inputs from industry experts. The report covers the ... report also includes a discussion of the key vendors operating in ...
(Date:6/22/2016)... June 22, 2016  The American College of Medical Genetics ... Executive Magazine as one of the fastest-growing trade shows ... at the Bellagio in Las Vegas . ... percentage of growth in each of the following categories: net ... and number of attendees. The 2015 ACMG Annual Meeting was ...
(Date:6/22/2016)... 2016   Acuant , the leading ... has partnered with RightCrowd ® to ... Management, Self-Service Kiosks and Continuous Workforce Assurance. ... functional enhancements to existing physical access control ... with an automated ID verification and authentication ...
Breaking Biology News(10 mins):
(Date:6/27/2016)... ... 27, 2016 , ... Rolf K. Hoffmann, former senior vice ... University of North Carolina Kenan-Flagler Business School effective June 27. , ... with a focus on the school’s international efforts, leading classes and participating in ...
(Date:6/24/2016)...  Regular discussions on a range of subjects including policies, ... entities said Poloz. Speaking at a lecture to ... he pointed to the country,s inflation target, which is set ... "In certain areas there needs ... economic goals, why not sit down and address strategy together?" ...
(Date:6/24/2016)... ... June 24, 2016 , ... Researchers at the Universita ... miRNAs in people with peritoneal or pleural mesothelioma. Their findings are the subject of ... now. , Diagnostic biomarkers are signposts in the blood, lung fluid or tissue ...
(Date:6/23/2016)... 2016   Boston Biomedical , an industry ... to target cancer stemness pathways, announced that its ... Drug Designation from the U.S. Food and Drug ... including gastroesophageal junction (GEJ) cancer. Napabucasin is an ... cancer stemness pathways by targeting STAT3, and is ...
Breaking Biology Technology: