Tripartite motif-containing protein 37 is an
E3 ubiquitin ligase
A ubiquitin ligase (also called an E3 ubiquitin ligase) is a protein that recruits an E2 ubiquitin-conjugating enzyme that has been loaded with ubiquitin, recognizes a protein substrate, and assists or directly catalyzes the transfer of ubiquitin ...
in humans that is encoded by the ''TRIM37''
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
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 ...
encodes a member of the
tripartite motif (TRIM) family, whose members are involved in diverse cellular functions such as developmental patterning and
oncogenesis
Carcinogenesis, also called oncogenesis or tumorigenesis, is the formation of a cancer, whereby normal cells are transformed into cancer cells. The process is characterized by changes at the cellular, genetic, and epigenetic levels and abnor ...
. The TRIM motif includes
zinc-binding domains, a RING finger region, a
B-box motif and a
coiled-coil domain. The RING finger and B-box domains chelate zinc and might be involved in protein–protein and/or protein–nucleic acid interactions. The gene mutations are associated with
mulibrey (muscle-liver-brain-eye) nanism, an autosomal recessive disorder that involves several tissues of
mesodermal
The mesoderm is the middle layer of the three germ layers that develops during gastrulation in the very early development of the embryo of most animals. The outer layer is the ectoderm, and the inner layer is the endoderm.Langman's Medical Embry ...
origin. Alternatively spliced transcript variants encoding the same protein have been identified.
It is responsible for the mono-
ubiquitination
Ubiquitin is a small (8.6 kDa) regulatory protein found in most tissues of eukaryotic organisms, i.e., it is found ''ubiquitously''. It was discovered in 1975 by Gideon Goldstein and further characterized throughout the late 1970s and 1980s. Fo ...
of
histone
In biology, histones are highly basic proteins abundant in lysine and arginine residues that are found in eukaryotic cell nuclei. They act as spools around which DNA winds to create structural units called nucleosomes. Nucleosomes in turn are wr ...
H2A at
lysine
Lysine (symbol Lys or K) is an α-amino acid that is a precursor to many proteins. It contains an α-amino group (which is in the protonated form under biological conditions), an α-carboxylic acid group (which is in the deprotonated −C ...
119, a modification commonly associated with
transcriptional repression.
Role in breast cancer
The 17q23 chromosomal region in which the ''TRIM37'' gene is located has been shown to be amplified in up to 40% of breast cancers.
The TRIM37 protein is thought to play a role in breast
cancer oncogenesis by ubiquitinating histone H2A in regions occupied by tumor-suppressing genes. This repression of tumor-suppressing genes increases the likelihood that a tumor will occur or that an existing tumor will be more aggressive.
Interactions
TRIM37 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
PRC1
Protein Regulator of cytokinesis 1 (PRC1) is a protein that in humans is encoded by the ''PRC1'' gene and is involved in cytokinesis.
Function
PRC1 protein is expressed at relatively high levels during S and G2/M phases of the cell cycle before ...
.
TRIM37 has also been shown to interact with PRC2 to alter its specificity, and when ''TRIM37'' is overexpressed, there are many changes to gene expression that lead to silencing of tumor-suppressing genes.
It has also been shown that TRIM37, PRC2, PRC1 work together to co-bind to target genes, resulting in their transcriptional repression. Knockdown of ''TRIM37'' expression via RNA-interference has shown to result in H2A becoming de-ubiquitinated and the dissociation of PRC1 and PRC2 from target genes. These changes allow the target gene to become transcriptionally active.
See also
*
Mulibrey nanism
Mulibrey nanism ("MUscle-LIver-BRain-EYe nanism") is a rare autosomal recessive congenital disorder. It causes severe growth failure along with abnormalities of the heart, muscle, liver, brain and eye. TRIM37 is responsible for various cellular ...
References
Further reading
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External links
* {{PDBe-KB2, O94972, E3 ubiquitin-protein ligase TRIM37