CD27 is a member of the
tumor necrosis factor receptor superfamily.
It is currently of interest to immunologists as a co-stimulatory
immune checkpoint molecule, and is the target of an anti-cancer drug in clinical trials.
Expression
During mouse embryonic development, specific (medium) expression levels of CD27 (in addition to high
cKit,
medium
Gata2,
and high
CD31 expression levels) define the very first adult definitive
hematopoietic stem cells generated in the
aorta-gonad-mesonephros region.
Furthermore, CD27 is expressed on both naïve and activated effector
T cells as well as
NK cells and activated
B cells.
It is a type I
transmembrane protein with cysteine-rich domains, but once T cells have become activated, a soluble form of CD27 can be shed.
Function
The protein encoded by this gene is a member of the
TNF-receptor superfamily.
This receptor is required for generation and long-term maintenance of
T cell immunity. It binds to ligand
CD70, and plays a key role in regulating B-cell activation and immunoglobulin synthesis.
When CD27 binds CD70, a signaling cascade leads to the differentiation and clonal expansion of T cells.
The cascade also results in improved survival and memory of
cytotoxic T cells and increased production of certain
cytokine
Cytokines are a broad and loose category of small proteins (~5–25 kDa) important in cell signaling. Cytokines are peptides and cannot cross the lipid bilayer of cells to enter the cytoplasm. Cytokines have been shown to be involved in a ...
s.
This receptor transduces signals that lead to the activation of
NF-κB
Nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) is a protein complex that controls transcription of DNA, cytokine production and cell survival. NF-κB is found in almost all animal cell types and is involved in cellular ...
and
MAPK8
Mitogen-activated protein kinase 8 (also known as JNK1) is a ubiquitous enzyme that in humans is encoded by the ''MAPK8'' gene.
Function
The protein encoded by this gene is a member of the MAP kinase and JNK family. MAP kinases act as an integ ...
/
JNK.
Adaptor proteins TRAF2, TRAF3, and TRAF5 have been shown to mediate the signaling process of this receptor via
ubiquitination.
CD27-binding protein (
SIVA
Siva may refer to:
Film and television
* Siva (director), Indian cinematographer and director
* ''Siva'' (1989 Tamil film), a film starring Rajinikanth as the title character
* ''Siva'' (1989 Telugu film), an action film
Music and dance
* "Siv ...
), a proapoptotic protein, can bind to this receptor and is thought to play an important role in the
apoptosis induced by this receptor.
In murine
γδ T cells
Gamma delta T cells (γδ T cells) are T cells that have a γδ T-cell receptor (TCR) on their surface. Most T cells are αβ (alpha beta) T cells with TCR composed of two glycoprotein chains called α (alpha) and β (beta) TCR chains. In contrast, ...
its expression has been correlated with the secretion of
IFNγ.
Clinical significance
As a drug target
Varlilumab is an
IgG1 antibody that binds to CD27 and is an experimental cancer treatment.
This agonist antibody stimulates CD27 when it binds.
The drug is in early clinical trials and appears to stimulate T cells and increase production of cytokines such as interferon-gamma.
Interactions
CD27 has been shown to
interact with
SIVA1,
and
TRAF3.
[
]
Mutations
Some mutations can decrease the expression of CD27. Three such mutations, C53Y, C96Y, and R107C, are located in the cysteine-rich domains of CD27.
References
Further reading
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External links
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