Fetal and Adult Testis-Expressed 1, encoded by the ''FATE1''

gene In biology, the word gene has two meanings. The Mendelian gene is a basic unit of heredity. The molecular gene is a sequence of nucleotides in DNA that is transcribed to produce a functional RNA. There are two types of molecular genes: protei ...

in humans, is a

protein Proteins are large biomolecules and macromolecules that comprise one or more long chains of amino acid residue (biochemistry), residues. Proteins perform a vast array of functions within organisms, including Enzyme catalysis, catalysing metab ...

identified as a cancer-testis antigen (CTA) in hepatocellular carcinomas and gastric and colon cancers. It is testis-specific in the

fetus A fetus or foetus (; : fetuses, foetuses, rarely feti or foeti) is the unborn offspring of a viviparous animal that develops from an embryo. Following the embryonic development, embryonic stage, the fetal stage of development takes place. Pren ...

(aged 6 – 11 weeks). In adults, it is expressed predominantly in the

testis A testicle or testis ( testes) is the gonad in all male bilaterians, including humans, and is Homology (biology), homologous to the ovary in females. Its primary functions are the production of sperm and the secretion of Androgen, androgens, p ...

and adrenal glands, with some expression in the lungs, heart, kidneys and throughout the brain. FATE1 is member of the

Miff MIFF may refer to: Film festivals * Listapad, aka Minsk International Film Festival, held each November in Minsk, Belarus * Maine International Film Festival, held in Waterville, Maine *Melbourne International Film Festival, held in Melbourne, A ...

protein family, with its C-terminal domain, consisting of a transmembrane domain with a coiled-coil domain, showing high similarity to the mitochondrial fission factor (MFF) protein which is involved in mitochondrial and peroxisomal fission.

Gene location

''FATE1'' gene in humans is located on the long arm of the

X chromosome The X chromosome is one of the two sex chromosomes in many organisms, including mammals, and is found in both males and females. It is a part of the XY sex-determination system and XO sex-determination system. The X chromosome was named for its u ...

at region 28, from

base pair A base pair (bp) is a fundamental unit of double-stranded nucleic acids consisting of two nucleobases bound to each other by hydrogen bonds. They form the building blocks of the DNA double helix and contribute to the folded structure of both DNA ...

150,884,502 to base pair 150,891,617.

Mechanism

It has been hypothesized that FATE1 uses its C-terminal transmembrane domain to attach to endoplasmic reticulum (ER) membrane and with its C-terminal

coiled-coil A coiled coil is a structural motif in proteins in which two to seven alpha-helices are coiled together like the strands of a rope. ( Dimers and trimers are the most common types.) They have been found in roughly 5-10% of proteins and have a v ...

domain it interacts with mitochondria. FATE1 is localized in mitochondria-associated ER membranes (MAM) and modulates ER-mitochondria distance to regulate Ca²⁺- and drug dependent apoptosis in cancer cells. FATE1 expression leads to reduction of Ca²⁺ uptake by mitochondria and therefore decrease in fragmentation of mitochondria, associated with mitochondrial Ca²⁺ uptake, consequently providing protection against cell death.

Relation to cancer

FATE1 is detectable in all cell lines derived from tumors, but is low or undetectable in telomere immortalized, non-tumorigenic fibroblasts and lung epithelial cells. FATE1 is suggested to be essential for survival of tumor cells as depletion of FATE1 results in viability reduction in melanoma, breast, prostate and sarcoma settings. Upregulation of FATE1 by a transcription factor steroidogenic factor-1 (SF-1), involved in adrenal and gonadal development as well as in adrenocortical carcinoma, increases ER-mitochondria distance and is utilized by cancer cell to functionally uncouple ER and mitochondria. Silencing ''FATE1'' gene sensitizes non-small-cell lung cancer cell lines to

paclitaxel Paclitaxel, sold under the brand name Taxol among others, is a chemotherapy medication used to treat ovarian cancer, esophageal cancer, breast cancer, lung cancer, Kaposi's sarcoma, cervical cancer, and pancreatic cancer. It is administered b ...

, a chemotherapeutic drug against many different types of cancers. Elevated level of FATE1 is found to be associated with higher mortality rate in colorectal cancers, but in non-small-cell lung cancers, elevation of FATE1 alone did not decrease chance of survival, but decreased if RNF183 expression is also increased.

Gene location

Mechanism

Relation to cancer

References

Further reading