Steroid Receptor Associated and Regulated Protein (SRARP) in humans 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, respon ...
encoded by a
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 ...
of the same name with two
exon
An exon is any part of a gene that will form a part of the final mature RNA produced by that gene after introns have been removed by RNA splicing. The term ''exon'' refers to both the DNA sequence within a gene and to the corresponding sequenc ...
s that is located on
chromosome 1p36.13. SRARP contains 169
amino acid
Amino acids are organic compounds that contain both amino and carboxylic acid functional groups. Although hundreds of amino acids exist in nature, by far the most important are the alpha-amino acids, which comprise proteins. Only 22 alpha ...
s and has a
molecular weight
A molecule is a group of two or more atoms held together by attractive forces known as chemical bonds; depending on context, the term may or may not include ions which satisfy this criterion. In quantum physics, organic chemistry, and bioch ...
of 17,657
Da.
Expression and function in breast cancer
SRARP is co-expressed with the
estrogen receptor
Estrogen receptors (ERs) are a group of proteins found inside cells. They are receptors that are activated by the hormone estrogen (17β-estradiol). Two classes of ER exist: nuclear estrogen receptors ( ERα and ERβ), which are members of th ...
(ER) and
androgen receptor (AR) in
breast cancer
Breast cancer is cancer that develops from breast tissue. Signs of breast cancer may include a lump in the breast, a change in breast shape, dimpling of the skin, milk rejection, fluid coming from the nipple, a newly inverted nipple, or ...
.
In the
ER-positive breast cancer cells, SRARP is involved in the transcriptional activities of ER and has shown an interaction with ER using the transient transfection of cells with SRARP and ER constructs.
In addition, in AR+ breast cancer cells, SRARP interacts with the endogenous AR protein and acts as a transcriptional
corepressor In the field of molecular biology, a corepressor is a molecule that represses the expression of genes. In prokaryotes, corepressors are small molecules whereas in eukaryotes, corepressors are proteins. A corepressor does not directly bind to DNA, ...
of AR.
Furthermore, the activation of either AR or ER negatively regulates SRARP expression in breast cancer cells.
Tumor suppressor function in malignancies
SRARP and HSPB7 are gene pairs that are positioned 5 kb apart on chromosome 1p36.13.
It is notable that the loss of chromosome 1p36.1 is common in malignancies, occurring in 34% of tumors
SRARP and HSPB7 are broadly inactivated in malignancies by epigenetic silencing, copy-number loss, and less frequently by somatic mutations.
In addition, overexpression of SRARP or HSPB7 leads to
tumor suppressor
A tumor suppressor gene (TSG), or anti-oncogene, is a gene that regulates a cell during cell division and replication. If the cell grows uncontrollably, it will result in cancer. When a tumor suppressor gene is mutated, it results in a loss or re ...
effects in cancer cell lines.
Another similar molecular feature between SRARP and HSPB7 is the fact that both of these proteins interact with the
14-3-3 protein
14-3-3 proteins are a family of conserved regulatory molecules that are expressed in all eukaryotic cells. 14-3-3 proteins have the ability to bind a multitude of functionally diverse signaling proteins, including kinases, phosphatases, and tran ...
.
Furthermore, SRARP is a potential
cancer biomarker
A cancer biomarker refers to a substance or process that is indicative of the presence of cancer in the body. A biomarker may be a molecule secreted by a tumor or a specific response of the body to the presence of cancer. Genetic, epigenetic, p ...
and SRARP inactivation predicts poor clinical outcome in malignancies and adjacent normal tissues using the analysis of large genomic datasets
References
{{Reflist
Proteins