One Renegade Cell (SCIENCE MASTERS) by Robert A Weinberg

Author:Robert A Weinberg [Weinberg, Robert A]
Language: eng
Format: epub, azw3
ISBN: 9781780227788
Publisher: Orion
Published: 2013-12-31T04:30:00+00:00

CHAPTER 10

GUIDE PROTEINS OF THE CELL: THE MACHINERY THAT CONTROLS GROWTH

Knowing about mutant genes allows us to trace the roots of cancer back to discrete, identifiable changes in the central controlling molecule of the cell, its DNA. But in one sense, these genetic discoveries are sterile and uninformative. Genes are pure information, nothing more than mathematical abstractions. Studied in isolation, they tell us little about the real life of the cell. Moreover, the sequence of DNA bases that constitutes a gene usually reveals little about how this gene operates. So, even after we know that one or another gene is mutated during the development of a cancer, we still understand next to nothing about the mechanisms by which this mutant gene causes abnormal cell growth. Fortunately, molecular biology provides us with a useful train of logic that leads us toward an understanding of gene function. Genes instruct the cells around them to make specific proteins. It is the proteins that do the work of the genes. Proteins catalyze biochemical reactions or create elaborate physical structures. To understand how a gene works, we must know intimately how its protein functions.

This logic dictates that each of the oncogenes described earlier encodes the structure of a specific protein. Once synthesized under the close supervision of its controlling gene, the oncogene protein sallies forth and effects changes in the cell. The src gene makes a protein termed pp60src, while ras makes as its product p21ras. The long list of oncogenes is paralleled by a corresponding catalog of oncogene proteins, sometimes termed oncoproteins. Of course, tumor suppressor genes also regulate cell proliferation through their own cohort of encoded proteins. In the end, a deep understanding of the disease of cancer can only come from detailed insight into how these various proteins operate.

Before we confront oncoproteins directly, we must place them in some biological context. In particular, we must learn how their normal counterparts contribute to the life of a normal, healthy cell. Normal cell function provides the baseline from which to study the molecular aberrations of cancer.

In one sense, the roles played by the normal versions of oncoproteins are obvious: They help the normal cell regulate its growth. Unfortunately, this statement does not take us very far; it only restates the problem, and in a way that is not terribly useful. A more productive tack is suggested by the following question: Precisely how do normal cells know when to grow and when to hold back from growth?

At any moment, the great majority of cells in our body are in a quiescent state. Only in tissues that renew themselves constantly, such as the colonic epithelium, the bone marrow (which generates new blood cells), and the skin, does one find large numbers of cells actively growing and dividing.

These dramatic differences in the proliferation rates of tissues bring us back to our question: Precisely how do any of these cells know when they should grow? The issue becomes even more complicated in the case of embryonic development, where

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