The key

To ensure proper functioning of an organism, living figs have "border control" systems - membranes that surround the entire cell and its various organelles and protect them from harmful substances.

Customs and border police are means that allow countries to monitor the movements of people, animals and goods. This supervision is essential to the fabric of life and the proper economy of the country. Similarly, to ensure the proper functioning of an organism, systems of "boundary control" operate in living cells - membranes that surround the entire cell and its various organelles and protect them from harmful substances. Thus, for example, the cell nucleus containing the cell's genetic cargo is surrounded by a double membrane that protects it and its cargo. This membrane regulates the flow of certain molecules from the cell body into the nucleus and vice versa. In this way, for example, the activation of genes in the nucleus is controlled, leading to the creation of the proteins required for the cell at the appropriate time and in the necessary quantities. For this purpose, there are "border crossings" in the nuclear membrane, the control of which allows the cell to prevent incorrect activation of the DNA, which could lead to the creation of damaged, unnecessary and even harmful proteins.

The molecules that have a suitable "passage certificate" can enter the nucleus to perform various "legitimate" actions in it. This "passage certificate" is, in fact, a kind of "location code" - a sequence of amino acids located in a certain region of the molecule. Special "transport proteins", called "importins", recognize this code, bind to it, and transport these molecules into the cell nucleus.

So far everything seems well organized. However, it recently became clear that certain molecules that do not carry the appropriate "passage certificate" nevertheless manage to pass the "inspection gate" and enter the nucleus.

In an article recently published in the scientific journal Molecular Cell, Weizmann Institute of Science scientists describe a mechanism responsible for the penetration of some of these molecules into the nucleus. These findings, the result of the research of Prof. Roni Zager, research student Dana Khuderland and post-doctoral researcher Dr. Alexander Kunson, from the Department of Biological Control at the Weizmann Institute of Science, may lead to the development of methods for new medical treatments.
The scientists focused on proteins that transmit signals, called ERKs. These proteins work mainly inside the nucleus, where they are involved, among other things, in the control of gene expression (which lead to the creation of specific proteins), in cell proliferation

and in their differentiation. Using various research techniques, including bioinformatic methods, the scientists discovered that these proteins nevertheless carry a unique "location code" with a sequence different from the known sequence. In fact, it turned out that the entry of

The nucleation of these molecules is more strictly controlled compared to the processes controlling the movement of other molecules. Thus, the ERK proteins "hold" their "passage certificate" when they themselves are anchored to other proteins in the intracellular space, which release them only when a signal is received from outside the cell (such as a growth factor or hormone). When such a protein is called for a journey in which it must cross the nuclear boundaries, its "passage certificate" must receive
A stamp of a phosphorus group (adding a phosphorus group to a protein, or reducing it, leads to a change in its structure or electrical charge, which changes its activity or its interactions with other proteins, and therefore serves as an important control mechanism on the protein's location and activity in the cell). Only after the protein has received the "passage stamp" can it bind a certain type of transport protein, which helps it settle in the nucleus and perform its function.

The scientists removed - using genetic engineering techniques - the entry code, thus preventing the addition of the phosphorus groups. As a result, these proteins were not transported into the nucleus, which inhibited the growth of the cells. ERK is not the only protein that uses this mechanism. Using bioinformatic means, the scientists found that about 40 proteins can enter the cell nucleus with the help of the new sequence (that is, in response to the arrival of a suitable signal outside the cell).

Prof. Zager says that these findings may be of great importance in the development of new treatment methods: incorrect activation of ERK proteins, which play an important role in the reproduction processes of cells, is a known factor in the development of cancerous tumors. Developing a drug that would selectively block the entry code sequence may interfere with the transport of the protein into the nucleus, and prevent cell culture. Such selective intervention will lead to more effective cancer treatment with fewer side effects.

in brief:

The question: How do the "border crossings" that supervise the movement of proteins between the cell nucleus and the cell body work?

The findings: Certain proteins carry sophisticated "passage certificates", which allow them to enter the nucleus only after being "stamped" with a phosphorus group, which occurs following the arrival of an appropriate signal from outside the cell - such as a growth factor or hormone.