F-box-like/WD repeat-containing protein TBL1XR1 is a
protein that in humans is encoded by the ''TBL1XR1''
gene.
The protein encoded by this gene has sequence similarity with members of the
WD40 repeat-containing protein family. The WD40 group is a large family of proteins that appear to have a
regulatory function. It is believed that the WD40 repeats mediate
protein–protein interactions, and members of the family are involved in
signal transduction
Signal transduction is the process by which a chemical or physical signal is transmitted through a cell as a series of molecular events, most commonly protein phosphorylation catalyzed by protein kinases, which ultimately results in a cellula ...
,
RNA processing, gene regulation, vesicular trafficking,
cytoskeletal assembly and may play a role in the control of cytotypic differentiation.
Clinical significance
Mutations in ''TBL1XR1'' cause
Pierpont syndrome Pierpont may refer to:
Surname
* Francis Harrison Pierpont (1814–1899), Governor of Virginia
* Harry Pierpont (1902–1934), Prohibition-era gangster
* James Pierpont (minister) (1659–1714), founder of Yale University
* James Lord Pierpont (1 ...
, which involves intellectual disability, a characteristic facial appearance and limb abnormalities.
Mutations in ''TBL1XR1'' have been identified in
lymphomas, including
MYD88 wild-type
Waldenstrom's macroglobulinemia.
In
prostate cancer
Prostate cancer is cancer of the prostate. Prostate cancer is the second most common cancerous tumor worldwide and is the fifth leading cause of cancer-related mortality among men. The prostate is a gland in the male reproductive system that sur ...
, somatic
copy-number gains (CNA) in ''TBL1XR1'' are present in around 15% of patients with localised disease, co-occurring with adjacent megagene ''
NAALADL2
N-Acetylated Alpha-Linked Acidic Dipeptidase Like 2 (NAALADL2) is a protein, encoded by the gene ''NAALADL2'' in humans. ''NAALADL2'' shares 25%–26% sequence identity and 45% sequence similarity with the glutamate carboxypeptidase II family which ...
''.
The frequency of
CNA gains in these genes associate with a number of clinical features of aggressive prostate cancer including high
Gleason grade
The Gleason grading system is used to help evaluate the prognosis of men with prostate cancer using samples from a prostate biopsy. Together with other parameters, it is incorporated into a strategy of prostate cancer staging which predicts prog ...
,
tumour stage
Cancer staging is the process of determining the extent to which a cancer has developed by growing and spreading. Contemporary practice is to assign a number from I to IV to a cancer, with I being an isolated cancer and IV being a cancer that ha ...
, positive
surgical margins and cancer which has spread to the
lymph node
A lymph node, or lymph gland, is a kidney-shaped organ of the lymphatic system and the adaptive immune system. A large number of lymph nodes are linked throughout the body by the lymphatic vessels. They are major sites of lymphocytes that inclu ...
s.
The frequency of copy-number gains in this genetic region also increase in
castrate resistant and
neuroendocrine prostate cancer.
The region surrounding ''TBL1XR1'' is rich in oncogenes. Copy-number gains in ''TBL1XR1'' often co-occur with neighbouring oncogenes including:
BCL6
Bcl-6 (B-cell lymphoma 6) is a protein that in humans is encoded by the ''BCL6'' gene. BCL6 is a master transcription factor for regulation of T follicular helper cells (TFH cells) proliferation. BCL6 has three evolutionary conserved structural do ...
, ATR and
PI3K family members. Copy-number gains at the DNA level associate with mRNA expression changes in more than 450 known oncogenes, suggesting this region may be important in driving aggressive prostate cancer.
''TBL1XR1'' is a co-activator of the
androgen receptor
The androgen receptor (AR), also known as NR3C4 (nuclear receptor subfamily 3, group C, member 4), is a type of nuclear receptor that is activated by binding any of the androgenic hormones, including testosterone and dihydrotestosterone in th ...
, a major hormone receptor driving prostate cancer development.
Of the genes whose expression was altered between patients with and without gains, 506 (14.09%) of the genes were androgen-regulated or contained an
AR binding site.
Interactions
TBL1XR1 has been shown to interact with
nuclear receptor co-repressor 1.
References
Further reading
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