Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Cell's Recycling Center Implicated in Division Decisions

29.07.2014

Allows cancer cells to divide even when oxygen-starved

Most cells do not divide unless there is enough oxygen present to support their offspring, but certain cancer cells and other cell types circumvent this rule.

Researchers at The Johns Hopkins University have now identified a mechanism that overrides the cells’ warning signals, enabling cancers to continue to divide even without a robust blood supply.

In the process, the researchers found that lysosomes — the cell’s protein “recycling centers” — help govern cell division decisions. They also uncovered new evidence that certain drugs can halt the growth of tumors that have high levels of the protein HIF-1alpha.

A summary of their findings will be published the week of July 28 in the journal PNAS.

Low levels of oxygen stimulate the production and activation of HIF-1alpha, which protects cells in two ways. Primarily, it turns on several genes for proteins that help the cells adapt to the lack of oxygen. It can also stop the duplication of DNA, which prevents cells from dividing and adding more oxygen-using cells to an already harsh environment.

Knowing that some cells ignore the warnings of HIF-1alpha and divide anyway, Gregg Semenza, M.D., Ph.D., and his team looked for interactions between HIF-1alpha and Cdk1 and Cdk2, proteins known to regulate cell division decisions. They found that HIF-1alpha interacts with both of them, but that Cdk1 increases HIF-1alpha levels, while Cdk2 lowers them.

Semenza’s team suspected that Cdk1 and Cdk2 were acting on HIF-1alpha by marking or not marking it for destruction by the cell’s miniature “garbage disposals,” called proteasomes. But when the researchers blocked proteasome function, they found no changes in HIF-1alpha levels.

Instead, Cdk1 and Cdk2 turned out to alter HIF-1alpha levels by marking or not marking it for destruction by the cell’s lysosomes. To their knowledge, this is the first time lysosomes have been implicated in a cell’s division decisions.

Remarkably, in certain cancer cells, Cdk2 was able to decrease levels of HIF-1alpha while also stimulating its gene activation activity. The net effect was that cells continued dividing while coping with low oxygen levels. In cultured cells, drugs that inhibit Cdk1 prevented HIF-1alpha levels from falling and restored its ability to halt cell division, suggesting they may be effective treatments for certain cancers.

Gregg Semenza is the C. Michael Armstrong Professor of Medicine and a professor of pediatrics, oncology, radiation oncology and biological chemistry at the Johns Hopkins University School of Medicine. Other authors of the report include Maimon Hubbi, Daniele Gilkes, Hongxia Hu and Ishrat Ahmed of the Johns Hopkins University School of Medicine; and Kshitiz of Yale University.

This work was supported by grants from the National Cancer Institute (K99CA181352) and the American Cancer Society.

Catherine Kolf | newswise
Further information:
http://www.jhmi.edu

Further reports about: Cancer Cdk1 Division Medicine Recycling Semenza activation destruction divide drugs levels lysosomes proteins

More articles from Life Sciences:

nachricht Cryo-electron microscopy achieves unprecedented resolution using new computational methods
24.03.2017 | DOE/Lawrence Berkeley National Laboratory

nachricht How cheetahs stay fit and healthy
24.03.2017 | Forschungsverbund Berlin e.V.

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

Die letzten 5 Focus-News des innovations-reports im Überblick:

Im Focus: Giant Magnetic Fields in the Universe

Astronomers from Bonn and Tautenburg in Thuringia (Germany) used the 100-m radio telescope at Effelsberg to observe several galaxy clusters. At the edges of these large accumulations of dark matter, stellar systems (galaxies), hot gas, and charged particles, they found magnetic fields that are exceptionally ordered over distances of many million light years. This makes them the most extended magnetic fields in the universe known so far.

The results will be published on March 22 in the journal „Astronomy & Astrophysics“.

Galaxy clusters are the largest gravitationally bound structures in the universe. With a typical extent of about 10 million light years, i.e. 100 times the...

Im Focus: Tracing down linear ubiquitination

Researchers at the Goethe University Frankfurt, together with partners from the University of Tübingen in Germany and Queen Mary University as well as Francis Crick Institute from London (UK) have developed a novel technology to decipher the secret ubiquitin code.

Ubiquitin is a small protein that can be linked to other cellular proteins, thereby controlling and modulating their functions. The attachment occurs in many...

Im Focus: Perovskite edges can be tuned for optoelectronic performance

Layered 2D material improves efficiency for solar cells and LEDs

In the eternal search for next generation high-efficiency solar cells and LEDs, scientists at Los Alamos National Laboratory and their partners are creating...

Im Focus: Polymer-coated silicon nanosheets as alternative to graphene: A perfect team for nanoelectronics

Silicon nanosheets are thin, two-dimensional layers with exceptional optoelectronic properties very similar to those of graphene. Albeit, the nanosheets are less stable. Now researchers at the Technical University of Munich (TUM) have, for the first time ever, produced a composite material combining silicon nanosheets and a polymer that is both UV-resistant and easy to process. This brings the scientists a significant step closer to industrial applications like flexible displays and photosensors.

Silicon nanosheets are thin, two-dimensional layers with exceptional optoelectronic properties very similar to those of graphene. Albeit, the nanosheets are...

Im Focus: Researchers Imitate Molecular Crowding in Cells

Enzymes behave differently in a test tube compared with the molecular scrum of a living cell. Chemists from the University of Basel have now been able to simulate these confined natural conditions in artificial vesicles for the first time. As reported in the academic journal Small, the results are offering better insight into the development of nanoreactors and artificial organelles.

Enzymes behave differently in a test tube compared with the molecular scrum of a living cell. Chemists from the University of Basel have now been able to...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

International Land Use Symposium ILUS 2017: Call for Abstracts and Registration open

20.03.2017 | Event News

CONNECT 2017: International congress on connective tissue

14.03.2017 | Event News

ICTM Conference: Turbine Construction between Big Data and Additive Manufacturing

07.03.2017 | Event News

 
Latest News

Argon is not the 'dope' for metallic hydrogen

24.03.2017 | Materials Sciences

Astronomers find unexpected, dust-obscured star formation in distant galaxy

24.03.2017 | Physics and Astronomy

Gravitational wave kicks monster black hole out of galactic core

24.03.2017 | Physics and Astronomy

VideoLinks
B2B-VideoLinks
More VideoLinks >>>