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Wednesday, January 09, 2008

Normal cellular counterparts of oncogenes

036. The normal cellular counterparts of oncogenes are important for the following functions except:

1. Promotion of cell cycle progression

2. Inhibition of apoptosis

3. Promotion of DNA repair

4. Promotion of nuclear transcription

Answer

3. Promotion of DNA repair

Reference:

Robbins 7th Edition Page 293, 295

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Discussion

An oncogene is a modified gene that increases the malignancy of a tumor cell. Some oncogenes, usually involved in early stages of cancer development, increase the chance that a normal cell develops into a tumor cell, possibly resulting in cancer. New research indicates that small RNAs 21-25 nucleotides in length called miRNAs can control expression of these genes by upregulating them.

The first oncogene was discovered in 1982 by Robert Weinberg, a founding member of Whitehead Institute for Biomedical Research and professor of biology at Massachusetts Institute of Technology.

Explanation

Genes involved in DNA repair are usually not associated with malignant transformation

Comments

A proto-oncogene is a normal gene that can become a oncogene, either after mutation or increased expression. They code for proteins that help to regulate cell growth and differentiation. Proto-oncogenes are often involved in signal transduction and execution of mitogenic signals, usually through its protein product. Upon activation, it (or its product) becomes a tumor inducing agent, an oncogene. The proto-oncogene can become an oncogene by a relatively small modification of its original function. There are two basic activation types:

Ä A mutation within a protooncogene can cause a change in the protein structure, caused by

o an increase in protein (enzyme) activity

o a loss of regulation

o the creation of a hybrid protein, through a chromosomal aberration during cell division. A distinct aberration in a dividing stem cell in the bone marrow leads to adult leukemia

Ä An increase in protein concentration, caused by

o an increase of protein expression (through misregulation)

o an increase of protein stability, prolonging its existence and thus its activity in the cell

o a gene duplication, resulting in an increased amount of protein in the cell

Tips

There are six known classes of protein kinases and related proteins that can become an oncogene:

1. Receptor tyrosine kinases that become constitutively (permanently) active like the epidermal growth factor receptor (EGFR), platelet-derived growth factor receptor (PDGFR), and vascular endothelial growth factor receptor (VEGFR).

2. Cytoplasmic tyrosine kinases like the Src-family, Syk-ZAP-70 family and BTK family of tyrosine kinases.

3. Regulatory GTPases, for example, the Ras protein.

4. Cytoplasmic Serine/Threonine kinases and their regulatory subunits, for example, the Raf kinase, and cyclin-dependent kinases (through overexpression).

5. Adaptor proteins in signal transduction.

6. Transcription factors.

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