Opioid growth factor receptor, also known as OGFr or the ζ-opioid receptor, is a
protein
Proteins are large biomolecules and macromolecules that comprise one or more long chains of amino acid residues. Proteins perform a vast array of functions within organisms, including catalysing metabolic reactions, DNA replication, res ...
which in humans is encoded by the ''OGFR''
gene
In biology, the word gene (from , ; "... Wilhelm Johannsen coined the word gene to describe the Mendelian units of heredity..." meaning ''generation'' or ''birth'' or ''gender'') can have several different meanings. The Mendelian gene is a b ...
.
The protein encoded by this gene is a
receptor
Receptor may refer to:
* Sensory receptor, in physiology, any structure which, on receiving environmental stimuli, produces an informative nerve impulse
*Receptor (biochemistry), in biochemistry, a protein molecule that receives and responds to a ...
for opioid growth factor (OGF), also known as
et(5)enkephalin. The endogenous ligand is thus a known
opioid peptide
Opioid peptides are peptides that bind to opioid receptors in the brain; opiates and opioids mimic the effect of these peptides. Such peptides may be produced by the body itself, for example endorphins. The effects of these peptides vary, but t ...
, and OGFr was originally discovered and named as a new
opioid receptor
Opioid receptors are a group of inhibitory G protein-coupled receptors with opioids as ligands. The endogenous opioids are dynorphins, enkephalins, endorphins, endomorphins and nociceptin. The opioid receptors are ~40% identical to somatostatin ...
zeta (ζ). However it was subsequently found that it shares little sequence similarity with the other opioid receptors, and has quite different function.
Function
The natural function of this receptor appears to be in regulation of tissue growth,
and it has been shown to be important in embryonic development,
wound repair,
and certain forms of cancer.
OGF is a negative regulator of cell proliferation and tissue organization in a variety of processes. The encoded unbound receptor for OGF has been localized to the outer nuclear envelope, where it binds OGF and is translocated into the nucleus. The coding sequence of this gene contains a polymorphic region of 60 nt tandem imperfect repeat units. Several transcripts containing between zero and eight repeat units have been reported.
Mechanism of activation
The opioid growth factor receptor consists of a chain of 677 amino acids, which includes a
nuclear localization sequence region. When OGF binds to the receptor, an OGF-OGFr complex is formed, which leads to the increase in the synthesis of the selective
cyclin-dependent kinase (CDK) inhibitor proteins, p12 and
p16
p16 (also known as p16INK4a, cyclin-dependent kinase inhibitor 2A, CDKN2A, multiple tumor suppressor 1 and numerous other synonyms), is a protein that slows cell division by slowing the progression of the cell cycle from the G1 phase to the S p ...
.
Retinoblastoma protein
The retinoblastoma protein (protein name abbreviated pRb; gene name abbreviated ''Rb'', ''RB'' or ''RB1'') is a proto-oncogenic tumor suppressor protein that is dysfunctional in several major cancers. One function of pRb is to prevent excessive ...
becomes inactivated through phosphorylation by CDKs, and leads to the progression of the cell cycle from the
G1 phase
The G1 phase, gap 1 phase, or growth 1 phase, is the first of four phases of the cell cycle that takes place in eukaryotic cell division. In this part of interphase, the cell synthesizes mRNA and proteins in preparation for subsequent steps lead ...
to the
S phase. Because the activation of the OGF receptor, blocks the phosphorylation of retinoblastoma proteins, retardation of the G
1 phase occurs, which prevents the cell from further dividing.
Therapeutic applications
Upregulation of OGFr and consequent stimulation of the OGF-OGFr system are important for the anti-proliferative effects of imidazoquinoline drugs like
imiquimod
Imiquimod, sold under the brand name Aldara among others, is a medication that acts as an immune response modifier that is used to treat genital warts, superficial basal cell carcinoma, and actinic keratosis. Scientists at 3M's pharmaceuticals ...
and
resiquimod, which are immune response modifiers with potent
antiviral
Antiviral drugs are a class of medication used for treating viral infections. Most antivirals target specific viruses, while a broad-spectrum antiviral is effective against a wide range of viruses. Unlike most antibiotics, antiviral drugs do no ...
and
antitumour
Chemotherapy (often abbreviated to chemo and sometimes CTX or CTx) is a type of cancer treatment that uses one or more anti-cancer drugs (chemotherapeutic agents or alkylating agents) as part of a standardized chemotherapy regimen. Chemotherap ...
effects, used as topical creams for the treatment of
skin cancer
Skin cancers are cancers that arise from the skin. They are due to the development of abnormal cells that have the ability to invade or spread to other parts of the body. There are three main types of skin cancers: basal-cell skin cancer (BCC) ...
s and
wart
Warts are typically small, rough, hard growths that are similar in color to the rest of the skin. They typically do not result in other symptoms, except when on the bottom of the feet, where they may be painful. While they usually occur on the ...
s.
Structure
OGF contains a
conserved N-terminal domain followed by a series of imperfect
repeats.
References
Further reading
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{{InterPro content, IPR006770
Protein families