Atrophin-1 is a protein that in humans is encoded by the ATN1 gene.[5] The encoded protein includes a serine repeat and a region of alternating acidic and basic amino acids, as well as the variable glutamine repeat.[6] The function of Atrophin-1 has not yet been determined.[7] There is evidence provided by studies of Atrophin-1 in animals to suggest it acts as a transcriptional co-repressor.[7] Atrophin-1 can be found in the nuclear and cytoplasmic compartments of neurons.[7] It is expressed in nervous tissue.[8]
The function of Atrophin-1 has not been defined yet. It is widely hypothesized that Atrophin-1 functions as a transcriptional co-repressor.[9] A transcriptional co-repressor is a protein that indirectly suppresses the activity of specific genes by interacting with DNA-binding proteins.[9]
The ATN1 gene has a segment of DNA called the CAG trinucleotide repeat.[9] It is made up of cytosine, adenine, and guanine.[9] The number of CAG repeats in the ATN1 gene in a healthy person will range from six to thirty-five repeats.[9] CAG repeats that exceed thirty-five can cause a gain-of-function mutation in ATN1.[10] Studies have supported the idea that mutated Atrophin-1 gathers in neurons and disrupts cell function.[11] The sequence of the ATN1 gene contains a nuclear localizing signal (NLS) and a nuclear export signal (NES).[11] It has been shown that a mutation of the NES in ATN1 can change where ATN1 localizes, and can cause aggregation to occur in the nucleus.[11] This can lead to an increase in cellular toxicity.[11]
Mutations in ATN1 are associated with a form of trinucleotide repeat disorder known as "dentatorubral-pallidoluysian atrophy" or "dentatorubropallidoluysian atrophy". Dentatorubral-pallidoluysian atrophy (DRPLA) is a rare neurodegenerative disorder characterized by cerebellar ataxia, myoclonic epilepsy, choreoathetosis, and dementia.[5] The disorder is related to the expansion of a trinucleotide repeat within this gene.[5]In patients with DRPLA, truncated ATN1 has been observed forming intranuclear aggregates that cause cell death.[11] The symptoms of this disorder can be credited to the significant reduction of brain and spinal tissue observed in those afflicted with DRPLA.[12] There are both juvenile-onset and late adult-onset variants of DRPLA, which show differing degrees of severity of specific symptoms.[12]
^Shen Y, Peterson AS (February 2009). "Atrophins' emerging roles in development and neurodegenerative disease". Cellular and Molecular Life Sciences. 66 (3): 437–46. doi:10.1007/s00018-008-8403-9. PMID18953689. S2CID11380927.
^ abcde"ATN1 gene". Genetics Home Reference. Retrieved 2017-02-21.
Yazawa I, Nukina N, Hashida H, Goto J, Yamada M, Kanazawa I (May 1995). "Abnormal gene product identified in hereditary dentatorubral-pallidoluysian atrophy (DRPLA) brain". Nature Genetics. 10 (1): 99–103. doi:10.1038/ng0595-99. PMID7647802. S2CID5850726.
Nagafuchi S, Yanagisawa H, Ohsaki E, Shirayama T, Tadokoro K, Inoue T, Yamada M (October 1994). "Structure and expression of the gene responsible for the triplet repeat disorder, dentatorubral and pallidoluysian atrophy (DRPLA)". Nature Genetics. 8 (2): 177–82. doi:10.1038/ng1094-177. PMID7842016. S2CID2590882.
Burke JR, Wingfield MS, Lewis KE, Roses AD, Lee JE, Hulette C, Pericak-Vance MA, Vance JM (August 1994). "The Haw River syndrome: dentatorubropallidoluysian atrophy (DRPLA) in an African-American family". Nature Genetics. 7 (4): 521–4. doi:10.1038/ng0894-521. PMID7951323. S2CID40759301.
Nagafuchi S, Yanagisawa H, Sato K, Shirayama T, Ohsaki E, Bundo M, Takeda T, Tadokoro K, Kondo I, Murayama N (January 1994). "Dentatorubral and pallidoluysian atrophy expansion of an unstable CAG trinucleotide on chromosome 12p". Nature Genetics. 6 (1): 14–8. doi:10.1038/ng0194-14. PMID8136826. S2CID19708585.
Koide R, Ikeuchi T, Onodera O, Tanaka H, Igarashi S, Endo K, Takahashi H, Kondo R, Ishikawa A, Hayashi T (January 1994). "Unstable expansion of CAG repeat in hereditary dentatorubral-pallidoluysian atrophy (DRPLA)". Nature Genetics. 6 (1): 9–13. doi:10.1038/ng0194-9. PMID8136840. S2CID27241147.
Takano T, Yamanouchi Y, Nagafuchi S, Yamada M (February 1996). "Assignment of the dentatorubral and pallidoluysian atrophy (DRPLA) gene to 12p 13.31 by fluorescence in situ hybridization". Genomics. 32 (1): 171–2. doi:10.1006/geno.1996.0100. PMID8786114.
