Oncogene



An oncogene is a gene that causes a cell to develop into a tumor cell.

Protooncogene

A protooncogene is a gene that is 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.

Activation

The protooncogene can become an oncogene by a relatively small modification
of its original function. There are two basic activation types:

   * 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
   * 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 a doubled amount of protein in
          the cell

Oncogene

Growth factors

Growth factors are usually secreted by few special cells to induce cell
proliferation in other cells. If a cell that usually does not produce growth
factors suddenly starts to do so (because it developed an oncogene), it will
thereby induce its own uncontrolled proliferation (autocrine loop), as well
as the proliferation of neighbouring cells.

Protein kinases

There are six known classes of tyrosine kinases that can become an oncogene:

  1. Receptor tyrosine kinases that become constitutive (permanently)
     active.
  2. Cytoplasmic tyrosine kinases, often products of viral oncogenes.
  3. Regulatory GTPases, for example, the Ras protein.
  4. Cytoplasmic Serine/Threonine kinases and their regulatory subunits, for
     example, the Raf kinase, and cyclines (through overexpression).
  5. Adaptor proteins in signal transduction.
  6. Transcription factors.

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