Growth arrest and DNA-damage-inducible protein GADD45 alpha 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, respo ...
that in humans is encoded by the ''GADD45A''
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 ba ...
.
Function
This gene is a member of a group of genes, the
GADD45 genes, whose transcript levels are increased following stressful growth arrest conditions and treatment with DNA-damaging agents (
mutagen
In genetics, a mutagen is a physical or chemical agent that permanently changes nucleic acid, genetic material, usually DNA, in an organism and thus increases the frequency of mutations above the natural background level. As many mutations can ca ...
s). The DNA damage-induced transcription of this gene is mediated by both
p53
p53, also known as Tumor protein P53, cellular tumor antigen p53 (UniProt name), or transformation-related protein 53 (TRP53) is a regulatory protein that is often mutated in human cancers. The p53 proteins (originally thought to be, and often s ...
-dependent and -independent mechanisms. The protein encoded by this gene responds to environmental stresses by mediating activation of the
p38/
JNK
c-Jun N-terminal kinases (JNKs), were originally identified as kinases that bind and phosphorylate c-Jun on Ser-63 and Ser-73 within its transcriptional activation domain. They belong to the mitogen-activated protein kinase family, and ar ...
pathway via
MTK1/MEKK4 kinase.
Applications
The fact that expression of this gene is an indicator of DNA damage has been exploited to construct an ''
in vitro
''In vitro'' (meaning in glass, or ''in the glass'') studies are performed with microorganisms, cells, or biological molecules outside their normal biological context. Colloquially called "test-tube experiments", these studies in biology an ...
'' test for
mutagenicity
In genetics, a mutagen is a physical or chemical agent that permanently changes genetic material, usually DNA, in an organism and thus increases the frequency of mutations above the natural background level. As many mutations can cause cancer in ...
, the GADD45a-GFP GreenScreen HC assay.
This assay consists of a cell line which has been engineered so that expression of GADD45A will lead to expression of
green fluorescent protein
The green fluorescent protein (GFP) is a protein that exhibits bright green fluorescence when exposed to light in the blue to ultraviolet range. The label ''GFP'' traditionally refers to the protein first isolated from the jellyfish ''Aequorea ...
, which can easily be detected. To test a substance for mutagenicity, it is applied to these cells and fluorescence is measured.
Interactions
GADD45A has been shown to
interact
Advocates for Informed Choice, dba interACT or interACT Advocates for Intersex Youth, is a 501(c)(3) nonprofit organization using innovative strategies to advocate for the legal and human rights of children with intersex traits. The organizati ...
with:
*
AURKA
Aurora kinase A also known as serine/threonine-protein kinase 6 is an enzyme that in humans is encoded by the ''AURKA'' gene.
Aurora A is a member of a family of mitotic serine/threonine kinases. It is implicated with important processes during m ...
,
*
Cdk1
Cyclin-dependent kinase 1 also known as CDK1 or cell division cycle protein 2 homolog is a highly conserved protein that functions as a serine/threonine protein kinase, and is a key player in cell cycle regulation. It has been highly studied in th ...
,
*
CCNB1,
[
* ]GADD45GIP1
Growth arrest and DNA-damage-inducible proteins-interacting protein 1 is a protein that in humans is encoded by the ''GADD45GIP1'' gene.
GADD45GIP1, also known as CRIF1 is newly identified de novo components in large subunit of mitoribosome. It i ...
MAP3K4
Mitogen-activated protein kinase kinase kinase 4 is an enzyme that in humans is encoded by the ''MAP3K4'' gene.
The central core of each mitogen-activated protein kinase (MAPK) pathway is a conserved cascade of 3 protein kinases: an activated MAPK ...
,P21
p21Cip1 (alternatively p21Waf1), also known as cyclin-dependent kinase inhibitor 1 or CDK-interacting protein 1, is a cyclin-dependent kinase inhibitor (CKI) that is capable of inhibiting all cyclin/CDK complexes, though is primarily associated ...
,PCNA
Proliferating cell nuclear antigen (PCNA) is a DNA clamp that acts as a processivity factor for DNA polymerase δ in eukaryotic cells and is essential for replication. PCNA is a homotrimer and achieves its processivity by encircling the DNA, whe ...
.
See also
* Gadd45
References
Further reading
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External links
*{{Commonscatinline