Leucine Zipper

A leucine zipper, (leucine scissors), is a super secondary structural motif found in proteins that creates adhesion forces in parallel alpha helices. It is a common dimerization domain found in some proteins involved in regulating gene expression.

Structure

The main feature of the leucine zipper domain is the predominance of the common amino acid leucine at the d position of the heptad repeat. Leucine zippers were first identified by sequence alignment of certain transcription factors which identified a common pattern of leucines every seven amino acids. These leucines were later shown to form the hydrophobic core of a coiled coil.

  Subscribe in a reader
FOS and AP1 Bound to DNA

Each half of a leucine zipper consists of a short alpha-helix with a leucine residue at every seventh position. The standard 3.6 residues per turn alpha-helix structure changes slightly to become a 3.5 residues per turn alpha-helix. Known also as the heptat repeat, one leucine comes in direct contact with another leucine on the other strand every second turn.

The bZip family of transcription factors consist of a basic region which interacts with the major groove of a DNA molecule through hydrogen bonding, and a hydrophobic leucine zipper region which is responsible for dimerization.

Leucine zipper regulatory proteins include c-fos and c-jun (the AP1 transcription factor), important regulators of normal development. If they are overproduced or mutated in a vital area, they may generate cancer. These proteins interact with the DNA as dimers (homo- or hetero-) and are also called basic zipper proteins (bZips).

Oncogenes

An oncogene is a protein-encoding gene which, when deregulated, participates in the onset and development of cancer. Genetic mutations resulting in the activation of oncogenes increase the chance that a normal cell will develop into a tumor cell. Oncogenes are figuratively thought to be in a perpetual tug-of-war with tumor suppressor genes which act to prevent DNA damage and keep the cell's activities under control. There is much evidence to support the notion that loss of tumor suppressors or gain of oncogenes can lead to cancer.

  Subscribe in a reader

Many cells normally undergo an apoptosis program. In the presence of an activated oncogene, disorderly survival and proliferation can be observed.[1] Most oncogenes require an additional step, such as mutations in another gene, or environmental factors, such as viral infection, to cause cancer. Since the 1970s, dozens of oncogenes have been identified in human cancer. Many new cancer drugs target those DNA sequences and their products.

A proto-oncogene is a normal gene that can become an oncogene due to mutations or increased expression. Proto-oncogenes 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 their protein products. Upon activation, a proto-oncogene (or its product) becomes a tumor-inducing agent, an oncogene.[5] Examples of proto-oncogenes include RAS, WNT, MYC, ERK and TRK.

Proto-oncogene

A proto-oncogene is a normal gene that can become an oncogene due to mutations or increased expression. Proto-oncogenes 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 their protein products. Upon activation, a proto-oncogene (or its product) becomes a tumor-inducing agent, an oncogene.Examples of proto-oncogenes include RAS, WNT, MYC, ERK and TRK.

free website hit counter code

From Proto-Oncogene To Oncogene

A proto-oncogene is a normal gene that can become an oncogene due to mutations or increased expression. Proto-oncogenes 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 their protein products. Upon activation, a proto-oncogene (or its product) becomes a tumor-inducing agent, an oncogene. Examples of proto-oncogenes include RAS, WNT, MYC, ERK and TRK.

  Subscribe in a reader
Conversion of proto-oncogenes
There are two mechanisms by which proto-oncogenes can be converted to cellular oncogenes:

Quantitative: Tumor formation is induced by an increase in the absolute number of proto-oncogene products or by its production in inappropriate cell types.

Qualitative: Conversion from proto-oncogene to transforming gene (c-onc) with changes in the nucleotide sequence which responsible for the acquisition of the new properties.