1. Cell Identity Determined by types and amounts of proteins in the cell
Protein identities and amounts controlled by gene expression
Differential gene expression leads to cell differentiation
Recall our earlier discussion about the difference between a skin cell and a heart cell. What makes them different? The types of proteins and the amounts of those proteins differentiate a skin cell from a heart cell. This is the case for all cells. It is the proteins that make the difference. As we have seen, gene expression is responsible for placing a protein in a cell. Therefore, cell identity is determined by the regulation of gene expression.

2. Differentiation Divide Differentiate Differentiating Cell Stem Cells
Stem cells are actively dividing, so the proteins important for cell division are present. In order to differentiate into something specific, like a nerve cell, one of the division products begins to change the types of proteins in the cell (meaning that nerve cell specific genes are activated and cell division genes are inactivated), while the other division product continues to have the same proteins in the cell and remains a stem cell. Once the cell finishes the change and becomes some type of mature tissue cell, like a nerve cell, it will continue to function as a tissue cell and rarely if ever divides.
Mature Tissue Cell

3. Blood Cell Differentiation
Blood cell differentiation is an excellent example. Blood cells come in many different types. Each type has a different function, and the functions can be extremely different. For example, an erythrocyte, or red blood cell, carries and delivers oxygen. That is about all it does. A T lymphocyte, or white blood cell, is a killer cell that destroys cells that have been infected. This is about all it does. Red blood cells are not killers and white blood cells do not carry and deliver oxygen. Explain how these cells differ from one another to allow this difference in function.

4. Regulating Gene Expression
Gene Expression Control b
a) transcription
b) processing
c) stabilization
d) translation
To differentiate, cells must change gene expression. There are many places along the gene expression pathway where regulation can occur. c
mRNA d
protein

5. Cell Must be Signaled to Change
Extracellular Signals
gene
1) Growth factors
2) Hormones
3) Cell-Cell contacts
Gene Expression
Control a b
a) transcription
b) processing
c) stabilization
d) translation
To change gene expression, a cell must be signaled by external communication molecules. These molecules are manufactured and secreted by one cell and detected by another (or the same) cell. There are many types of these communication molecules. Growth factors, like human growth hormone (HGH), hormones, like steroid hormones and direct cell to cell communication by contact are some examples of the signals that can change gene expression. c
mRNA d
protein

6. Types of Signaling
The way signals are produced and detected are classified by the distance that the signal travels. Direct contacts are one class. Secreted molecules that are detected by another cell represent another class. Within the secreted molecule class, you can further distinguish long distance communication (endocrine) from neighboring cell communication (paracrine) from same cell communication (autocrine). Notice that in each case, the signaling molecule is detected by interaction with a receptor at the cell surface. When the signaling molecule binds to the receptor, the cell must communicate the signal to the proper molecules and components on the interior of the cell. This communication is called signal transduction.

7. Example-Ras Signal Transduction
Binding of the communication molecule (hormone) causes binding of communication proteins inside the cell (Ras). When Ras binds, it binds other proteins (SOS, Grb2), which activates the Ras protein (by a chemical change). This initiates a series of chemical changes in a sequential pathway until transcription factors are activated in the nucleus. These activated transcription factors then activate specific genes in the chromatin and gene expression changes.
Zbigniew Walaszek et al,
Cellscience Reviews
Vol 1, No

8. Ras Signal Transduction
doi: /nbt
Nature Biotechnology 26, (2008)
Malorye Allison
Ras Signal Transduction
Every signal transduction pathway, such as the one for Ras, has turned out to be extremely complicated and highly branched. In fact it is more like a web than a sequential pathway. The figure shows just some of the complexities of the Ras signaling web. Notice that the result of Ras signaling is primarily about issues of cell division. Proliferation is cell division, apoptosis is cell suicide, angiogenesis is construction of blood vessels, survival is longevity, and metastasis is the ability to spread. Would you expect Ras to be active in a stem cell or in a differentiated tissue cell? Would you expect Ras to active in a cancer cell?
Malorye Allison Nature Biotechnology 26, (2008)doi: /nbt

9. Signal Transduction Complexity
Notice position of Ras pathway. Also notice how all of these pathways are primarily influencing cell division (proliferation) and cell death (apoptosis). This proves that the decision that a cell makes to divide or even to survive is regulated extremely carefully. In fact there are incredibly sophisticated mechanisms to ensure that the decision to divide is the correct one. Cells that have lost their ability to control this decision are cancer cells and it is clear how devastating that situation is for the organism.

10. Cell Division Fundamental property of living things
Incredibly complicated process
Cell must ensure coordination of growth, genome duplication and cell division
Must not enter duplication cycle unless resources are plentiful
Must not divide before genome is completely duplicated

11. Cell Cycle Division process takes about 24 hours in humans
Just after division a cell must go through a period of growth and accumulation of materials. This is called gap 1 phase or G1. At the end of G1, a cell makes the decision to proceed with division and initiates the duplication of the genome, this phase is called synthesis or S. After the genome has been completely copied, the cell enters a period of preparation for division called gap 2 or G2. At the end of G2, the cell segregates the copies of the genome and divides, this is called mitosis or M.

12. Signals and Transduction Drives Cell Cycle

13. Cell Cycle can be Stopped

14. Example, Tumor Suppressor p53
DNA damage causes
p53 to be activated.
p53 blocks cell cycle

15. How Does Cancer Happen?
Mutations that incorrectly activate any protein in the Ras pathway can cause loss of cell cycle regulation
EGF, ErbB, Ras, Raf, Mek, Erk, Elk, Srf, Fos
But what about p53?

16. p53 is also Mutated
Over 50% of human tumors have p53 mutations

17. Multiple Events Required for Cancer
Alterations in the pathway of colon cancer are well known

18. Bioinformatics Contributes to our Understanding
cropwiki.irri.org/.../2/23/Bioinformatics2.jpg