Oncogenes-by localization of their products

An oncogene is a gene that when mutated or expressed at abnormally-high levels contributes to converting a normal cell into a cancer cell. Cancer cells are cells that are engaged in uncontrolled mitosis. The products of oncogenes can be classified into six broad groups: transcription factor chromatin remodelers growth factors or mitogens growth factor receptors signal transducers apoptosis regulators

Transcription Factors Transcription factors are often members of multigene families that share common structural domains. To act, many transcription factors require interaction with other proteins. In some tumors, for example, the Fos transcription protein dimerizes with the Jun transcription factor to form the AP1 transcription factor, and this complex increases the expression of several genes that control cell division. Chromatin Remodelers Modifications in the degree of compaction of chromatin play a critical role in the control of gene expression, replication, and repair and of chromosome segregation. Two kinds of enzymes remodel chromatin: ATP-dependent enzymes that move the positions of nucleosomes, the repeating subunits of the histones in chromatin around which DNA winds, and enzymes that modify the N-terminal tails of histones. The pattern of histone modification constitutes an epigenetic code that determines the interaction between nucleosomes and chromatin-associated proteins. These interactions, in turn, determine the structure of chromatin and its transcriptional capacity.

Growth factors, or mitogens Usually secreted by specialized cells to induce cell proliferation in themselves, nearby cells, or distant cells. An oncogene may cause a cell to secrete growth factors even though it does not normally do so. It will thereby induce its own uncontrolled proliferation (autocrine loop), and proliferation of neighboring cells. It may also cause production of growth hormones in other parts of the body. Growth Factor Receptors Growth factor receptors are altered in many cancers. In many tumors, a deletion of the ligand-binding domain of epidermal growth factor receptor (EGFR), a transmembrane protein with tyrosine kinase activity, causes constitutive activation of the receptor in the absence of ligand binding.

Growth factors (purple and yellow) bind to receptors (blue and green) that protrude from a cell's surface. A cross-section view shows how the opposite end of each receptor reaches the inside of the cell (deep red area)

Signal Transducers Binding of receptor tyrosine kinases to the appropriate ligand causes reorganization of the receptors and autophosphorylation of tyrosines in the intracellular portion of the molecules. -Receptor tyrosine kinases Kinases add phosphate groups to other proteins to turn them on or off. Receptor kinases add phosphate groups to receptor proteins at the surface of the cell (which receive protein signals from outside the cell and transmit them to the inside of the cell). Tyrosine kinases add phosphate groups to the amino acid tyrosine in the target

protein. They can cause cancer by turning the receptor permanently on (constitutively), even without signals from outside the cell.

Apoptosis Regulators The BCL2 gene, which is involved in the initiation of almost all follicular lymphomas and some diffuse large B-cell lymphomas, encodes a cytoplasmic protein that localizes to mitochondria and increases cell survival by inhibiting apoptosis. BCL2 is also important in chronic lymphocytic leukemia and lung cancer.