Opioid growth factor receptor, also known as OGFr or the ζ-opioid receptor, is a
protein which in humans is encoded by the ''OGFR''
gene.
The protein encoded by this gene is a
receptor for opioid growth factor (OGF), also known as
et(5)enkephalin. The endogenous ligand is thus a known
opioid peptide, and OGFr was originally discovered and named as a new
opioid receptor 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 A nuclear localization signal ''or'' sequence (NLS) is an amino acid sequence that 'tags' a protein for import into the cell nucleus by nuclear transport. Typically, this signal consists of one or more short sequences of positively charged lysines o ...
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
Cyclin-dependent kinases (CDKs) are the families of protein kinases first discovered for their role in regulating the cell cycle. They are also involved in regulating transcription, mRNA processing, and the differentiation of nerve cells. They a ...
(CDK) inhibitor proteins, p12 and
p16.
Retinoblastoma protein becomes inactivated through phosphorylation by CDKs, and leads to the progression of the cell cycle from the
G1 phase to the
S phase
S phase (Synthesis Phase) is the phase of the cell cycle in which DNA is replicated, occurring between G1 phase and G2 phase. Since accurate duplication of the genome is critical to successful cell division, the processes that occur during ...
. 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 and
resiquimod
Resiquimod (R-848) is a drug that acts as an immune response modifier, and has Antiviral drug, antiviral and antitumour activity. It is used as a topical gel in the treatment of skin lesions such as those caused by the herpes simplex virus and cu ...
, which are immune response modifiers with potent
antiviral and
antitumour effects, used as topical creams for the treatment of
skin cancers and
warts.
Structure
OGF contains a
conserved N-terminal
The N-terminus (also known as the amino-terminus, NH2-terminus, N-terminal end or amine-terminus) is the start of a protein or polypeptide, referring to the free amine group (-NH2) located at the end of a polypeptide. Within a peptide, the ami ...
domain
Domain may refer to:
Mathematics
*Domain of a function, the set of input values for which the (total) function is defined
**Domain of definition of a partial function
**Natural domain of a partial function
**Domain of holomorphy of a function
* Do ...
followed by a series of imperfect
repeat
Repeat may refer to:
* Rerun, a rebroadcast of an episode of a radio or television program
* Repeated sequence (DNA), a pattern of nucleic acid (DNA or RNA) that occurs in multiple copies throughout the genome
** CRISPR
* The smallest rectangle ...
s.
References
Further reading
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{{InterPro content, IPR006770
Protein families