FET protein family

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The FET protein family (also known as the TET protein family) [1] consists of three similarly structured and functioning proteins. [2] They and the genes in the FET gene family which encode them (i.e. form the pre-messenger RNAs that are converted to the messenger RNAs responsible for their production) are: [2] [3] 1) the EWSR1 protein encoded by the EWSR1 gene (also termed the Ewing sarcoma RNA binding protein, EWS RNA binding protein 1, or bK984G1.4 gene) located at band 12.2 of the long (i.e. "q") arm of chromosome 22; [4] 2) the FUS (i.e. fused in sarcoma) protein encoded by the FUS gene (also termed the FUS RNA binding protein, TLS, asTLS, ALS6, ETM4, FUS1, POMP75, altFUS, or HNRNPP2 gene) located at band 16 on the short arm of chromosome 16; [5] and 3) the TAF15 protein encoded by the TAF15 gene (also termed the TATA-box binding protein associated factor 15, Npl3, RBP56, TAF2N, or TAFII68 gene) located at band 12 on the long arm of chromosome 7 [6] The FET in this protein family's name derives from the first letters of FUS, EWSR1, and TAF15. [7]

Contents

FET proteins are abundantly expressed in virtually all tissues examined. They are RNA-binding proteins. [7] By binding to their RNA targets, they contribute to the regulation of: a) the transcription of genes into pre-messenger RNA, the splicing of pre-messenger RNA into mature messenger RNA, and the transport of these RNAs between different areas of their parent cells; b) the processing of micro-RNAs that are involved in RNA silencing and post-transcriptional regulation of gene expression; and 3) the detection and repair of damaged DNA. Through these multiple, complex, and often incompletely understood actions, the FET family proteins regulate the cellular expression of diverse genes. [2] However, the genes for FET proteins often undergo various types of mutation. While these mutations and the diseases with which they are associated can be found in the Wikipedia pages on these diseases, this article focuses on one type of mutation, the fusion gene mutation. Fusion genes are formed from two previously independent genes that become united due to a chromosome translocation, deletion of some genetic material in a chromosome, or chromosomal inversion. [1] [8] For example, the EWSR1-FL1 [9] fusion gene is made by a chromosomal translocation which merges part of the EWSR1 gene normally located on band 12 of the long (or "q") arm of chromosome 22 with part of the FLI1 ETS transcription factor family gene normally located on band 24 of the long arm of chromosome 11. The EWSR1-FLI1 fusion gene encodes an EWS-FLI1 chimeric protein which possesses unregulated and excessive FLI1 transcription factor activity which it appears to contribute to the development of Ewing sarcomas. [10] FET fusion genes have attracted recent interest because they have been found to be associated with, and may act to promote the development of, a wide range of soft tissue neoplasms derived from mesencyhmal tissue cells. [3] [7] [11] Detection of a FET gene–containing fusion gene is extremely helpful in diagnosing tumor types, [1] [11] defining the pathogenic mechanisms by which these fusion proteins promote disorders, [3] [12] and thereby identifying potential targets for treating these disorders. [2] [13] The following are examples of these fusion genes' associations with malignant and benign neoplastic tumors. [1] [7]

Malignant neoplasms

Benign neoplasms

Related Research Articles

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<span class="mw-page-title-main">Desmoplastic small-round-cell tumor</span> Aggressive and rare cancer

Desmoplastic small-round-cell tumor (DSRCT) is an aggressive and rare cancer that primarily occurs as masses in the abdomen. Other areas affected may include the lymph nodes, the lining of the abdomen, diaphragm, spleen, liver, chest wall, skull, spinal cord, large intestine, small intestine, bladder, brain, lungs, testicles, ovaries, and the pelvis. Reported sites of metastatic spread include the liver, lungs, lymph nodes, brain, skull, and bones. It is characterized by the EWS-WT1 fusion protein.

<span class="mw-page-title-main">Ewing sarcoma</span> Type of cancer

Ewing sarcoma is a type of pediatric cancer that forms in bone or soft tissue. Symptoms may include swelling and pain at the site of the tumor, fever, and a bone fracture. The most common areas where it begins are the legs, pelvis, and chest wall. In about 25% of cases, the cancer has already spread to other parts of the body at the time of diagnosis. Complications may include a pleural effusion or paraplegia.

<span class="mw-page-title-main">RNA-binding protein EWS</span> Human protein and coding gene

RNA-binding protein EWS is a protein that in humans is encoded by the EWSR1 gene on human chromosome 22, specifically 22q12.2. It is one of 3 proteins in the FET protein family.

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<span class="mw-page-title-main">RNA-binding protein FUS</span> Human protein and coding gene

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<span class="mw-page-title-main">Endometrial stromal sarcoma</span> Medical condition

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<span class="mw-page-title-main">Low-grade fibromyxoid sarcoma</span> Medical condition

Low-grade fibromyxoid sarcoma (LGFMS) is a rare type of low-grade sarcoma first described by H. L. Evans in 1987. LGFMS are soft tissue tumors of the mesenchyme-derived connective tissues; on microscopic examination, they are found to be composed of spindle-shaped cells that resemble fibroblasts. These fibroblastic, spindle-shaped cells are neoplastic cells that in most cases of LGFMS express fusion genes, i.e. genes composed of parts of two different genes that form as a result of mutations. The World Health Organization (2020) classified LGFMS as a specific type of tumor in the category of malignant fibroblastic and myofibroblastic tumors.

<span class="mw-page-title-main">Inflammatory myofibroblastic tumour</span> Medical condition

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<span class="mw-page-title-main">Unicameral bone cyst</span> Medical condition

A unicameral bone cyst, also known as a simple bone cyst, is a cavity filled with a yellow-colored fluid. It is considered to be benign since it does not spread beyond the bone. Unicameral bone cysts can be classified into two categories: active and latent. An active cyst is adjacent to the epiphyseal plate and tends to grow until it fills the entire diaphysis, the shaft, of the bone; depending on the invasiveness of the cyst, it can cause a pathological fracture or even destroy the epiphyseal plate leading to the permanent shortening of the bone.

<span class="mw-page-title-main">Angiomatoid fibrous histiocytoma</span> Type of tumor which affects children and adolescents

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<span class="mw-page-title-main">CREB3L1</span> Protein-coding gene in the species Homo sapiens

CAMP responsive element binding protein 3 like 1 is a responsive element binding protein that in humans is encoded by the CREB3L1 gene.

Acral myxoinflammatory fibroblastic sarcoma (AMSF), also termed myxoinflammatory fibroblastic sarcoma (MSF), is a rare, low-grade, soft tissue tumor that the World Health Organization (2020) classified as in the category of rarely metastasizing fibroblastic and myofibroblastic tumors. It is a locally aggressive neoplasm that often recurs at the site of its surgical removal. However, it usually grows slowly and in only 1–2% of cases spreads to distant tissues.

EWS/FLI1 is an oncogenic protein that is pathognomonic for Ewing sarcoma. It is found in approximately 90% of all Ewing sarcoma tumors with the remaining 10% of fusions substituting one fusion partner with a closely related family member.

<span class="mw-page-title-main">Proliferative fasciitis and proliferative myositis</span> Medical condition

Proliferative fasciitis and proliferative myositis (PF/PM) are rare benign soft tissue lesions that increase in size over several weeks and often regress over the ensuing 1–3 months. The lesions in PF/PM are typically obvious tumors or swellings. Historically, many studies had grouped the two descriptive forms of PF/PM as similar disorders with the exception that proliferative fasciitis occurs in subcutaneous tissues while proliferative myositis occurs in muscle tissues. In 2020, the World Health Organization agreed with this view and defined these lesions as virtually identical disorders termed proliferative fasciitis/proliferative myositis or proliferative fasciitis and proliferative myositis. The Organization also classified them as one of the various forms of the fibroblastic and myofibroblastic tumors.

Sclerosing epithelioid fibrosarcoma (SEF) is a very rare malignant tumor of soft tissues that on microscopic examination consists of small round or ovoid neoplastic epithelioid fibroblast-like cells, i.e. cells that have features resembling both epithelioid cells and fibroblasts. In 2020, the World Health Organization classified SEF as a distinct tumor type in the category of malignant fibroblastic and myofibroblastic tumors. However, current studies have reported that low-grade fibromyxoid sarcoma (LGFMS) has many clinically and pathologically important features characteristic of SEF; these studies suggest that LGSFMS may be an early form of, and over time progress to become, a SEF. Since the World Health Organization has classified LGFMS as one of the malignant fibroblastic and myofibroblastic tumors that is distinctly different than SEF, SEF and LGFMS are here regarded as different tumor forms.

Angiofibroma of soft tissue (AFST), also termed angiofibroma, not otherwise specified, is a recently recognized and rare disorder that was classified in the category of benign fibroblastic and myofibroblastic tumors by the World Health Organization in 2020. An AFST tumor is a neoplasm that was first described by A. Mariño-Enríquez and C.D. Fletcher in 2012.

References

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