Tripartite motif-containing protein 37 is an E3 ubiquitin ligase in humans that is encoded by the TRIM37gene.[5][6][7][8]
Function
This gene encodes a member of the tripartite motif (TRIM) family, whose members are involved in diverse cellular functions such as developmental patterning and oncogenesis. The TRIM motif includes zinc-binding domains, a RING finger region, a B-box motif and a coiled-coil domain. The RING finger and B-box domains chelate zinc and might be involved in protein–protein and/or protein–nucleic acid interactions. The gene mutations are associated with mulibrey (muscle-liver-brain-eye) nanism, an autosomal recessive disorder that involves several tissues of mesodermal origin. Alternatively spliced transcript variants encoding the same protein have been identified.[7] It is responsible for the mono-ubiquitination of histone H2A at lysine 119, a modification commonly associated with transcriptional repression.[8][9]
Role in breast cancer
The 17q23 chromosomal region in which the TRIM37 gene is located has been shown to be amplified in up to 40% of breast cancers.[10] The TRIM37 protein is thought to play a role in breast cancer oncogenesis by ubiquitinating histone H2A in regions occupied by tumor-suppressing genes. This repression of tumor-suppressing genes increases the likelihood that a tumor will occur or that an existing tumor will be more aggressive.[8]
Interactions
TRIM37 has been shown to interact with PRC1.[11] TRIM37 has also been shown to interact with PRC2 to alter its specificity, and when TRIM37 is overexpressed, there are many changes to gene expression that lead to silencing of tumor-suppressing genes.[8] It has also been shown that TRIM37, PRC2, PRC1 work together to co-bind to target genes, resulting in their transcriptional repression. Knockdown of TRIM37 expression via RNA-interference has shown to result in H2A becoming de-ubiquitinated and the dissociation of PRC1 and PRC2 from target genes. These changes allow the target gene to become transcriptionally active.[8]
^ a b cGRCh38: Ensembl release 89: ENSG00000108395 – Ensembl, May 2017
^ a b cGRCm38: Ensembl release 89: ENSMUSG00000018548 – Ensembl, May 2017
^"Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
^"Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
^Avela K, Lipsanen-Nyman M, Perheentupa J, Wallgren-Pettersson C, Marchand S, Fauré S, et al. (April 1997). "Assignment of the mulibrey nanism gene to 17q by linkage and linkage-disequilibrium analysis". American Journal of Human Genetics. 60 (4): 896–902. PMC1712467. PMID 9106536.
^Avela K, Lipsanen-Nyman M, Idänheimo N, Seemanová E, Rosengren S, Mäkelä TP, et al. (July 2000). "Gene encoding a new RING-B-box-Coiled-coil protein is mutated in mulibrey nanism". Nature Genetics. 25 (3): 298–301. doi:10.1038/77053. PMID 10888877. S2CID 24257747.
^ a b"Entrez Gene: TRIM37 tripartite motif-containing 37".
^ a b c d eBhatnagar S, Gazin C, Chamberlain L, Ou J, Zhu X, Tushir JS, et al. (December 2014). "TRIM37 is a new histone H2A ubiquitin ligase and breast cancer oncoprotein". Nature. 516 (7529): 116–20. Bibcode:2014Natur.516..116B. doi:10.1038/nature13955. PMC4269325. PMID 25470042.
^Sinclair, Colleen S.; Rowley, Matthew; Naderi, Ali; Couch, Fergus J. (2003-04-01). "The 17q23 Amplicon and Breast Cancer". Breast Cancer Research and Treatment. 78 (3): 313–322. doi:10.1023/A:1023081624133. ISSN 1573-7217. PMID 12755490. S2CID 23751525.
^Rual JF, Venkatesan K, Hao T, Hirozane-Kishikawa T, Dricot A, Li N, et al. (October 2005). "Towards a proteome-scale map of the human protein-protein interaction network". Nature. 437 (7062): 1173–8. Bibcode:2005Natur.437.1173R. doi:10.1038/nature04209. PMID 16189514. S2CID 4427026.
Further reading
Nagase T, Ishikawa K, Suyama M, Kikuno R, Hirosawa M, Miyajima N, et al. (December 1998). "Prediction of the coding sequences of unidentified human genes. XII. The complete sequences of 100 new cDNA clones from brain which code for large proteins in vitro". DNA Research. 5 (6): 355–64. doi:10.1093/dnares/5.6.355. PMID 10048485.
Zapata JM, Pawlowski K, Haas E, Ware CF, Godzik A, Reed JC (June 2001). "A diverse family of proteins containing tumor necrosis factor receptor-associated factor domains". The Journal of Biological Chemistry. 276 (26): 24242–52. doi:10.1074/jbc.M100354200. PMID 11279055.
Reymond A, Meroni G, Fantozzi A, Merla G, Cairo S, Luzi L, et al. (May 2001). "The tripartite motif family identifies cell compartments". The EMBO Journal. 20 (9): 2140–51. doi:10.1093/emboj/20.9.2140. PMC125245. PMID 11331580.
Lehesjoki AE, Reed VA, Mark Gardiner R, Greene ND (October 2001). "Expression of MUL, a gene encoding a novel RBCC family ring-finger protein, in human and mouse embryogenesis". Mechanisms of Development. 108 (1–2): 221–5. doi:10.1016/S0925-4773(01)00491-9. PMID 11578880. S2CID 15474684.
Kallijärvi J, Avela K, Lipsanen-Nyman M, Ulmanen I, Lehesjoki AE (May 2002). "The TRIM37 gene encodes a peroxisomal RING-B-box-coiled-coil protein: classification of mulibrey nanism as a new peroxisomal disorder". American Journal of Human Genetics. 70 (5): 1215–28. doi:10.1086/340256. PMC447596. PMID 11938494.
Jagiello P, Hammans C, Wieczorek S, Arning L, Stefanski A, Strehl H, et al. (June 2003). "A novel splice site mutation in the TRIM37 gene causes mulibrey nanism in a Turkish family with phenotypic heterogeneity". Human Mutation. 21 (6): 630–5. doi:10.1002/humu.10220. PMID 12754710. S2CID 24074182.
Hämäläinen RH, Avela K, Lambert JA, Kallijärvi J, Eyaid W, Gronau J, et al. (May 2004). "Novel mutations in the TRIM37 gene in Mulibrey Nanism". Human Mutation. 23 (5): 522. doi:10.1002/humu.9233. PMID 15108285. S2CID 22994120.
Kallijärvi J, Lahtinen U, Hämäläinen R, Lipsanen-Nyman M, Palvimo JJ, Lehesjoki AE (August 2005). "TRIM37 defective in mulibrey nanism is a novel RING finger ubiquitin E3 ligase". Experimental Cell Research. 308 (1): 146–55. doi:10.1016/j.yexcr.2005.04.001. PMID 15885686.
Rual JF, Venkatesan K, Hao T, Hirozane-Kishikawa T, Dricot A, Li N, et al. (October 2005). "Towards a proteome-scale map of the human protein-protein interaction network". Nature. 437 (7062): 1173–8. Bibcode:2005Natur.437.1173R. doi:10.1038/nature04209. PMID 16189514. S2CID 4427026.
Karlberg N, Jalanko H, Kallijärvi J, Lehesjoki AE, Lipsanen-Nyman M (December 2005). "Insulin resistance syndrome in subjects with mutated RING finger protein TRIM37". Diabetes. 54 (12): 3577–81. doi:10.2337/diabetes.54.12.3577. PMID 16306379.
Hämäläinen RH, Joensuu T, Kallijärvi J, Lehesjoki AE (January 2006). "Characterisation of the mulibrey nanism-associated TRIM37 gene: transcription initiation, promoter region and alternative splicing". Gene. 366 (1): 180–8. doi:10.1016/j.gene.2005.08.008. PMID 16310976.
Lim J, Hao T, Shaw C, Patel AJ, Szabó G, Rual JF, et al. (May 2006). "A protein-protein interaction network for human inherited ataxias and disorders of Purkinje cell degeneration". Cell. 125 (4): 801–14. doi:10.1016/j.cell.2006.03.032. PMID 16713569. S2CID 13709685.
Olsen JV, Blagoev B, Gnad F, Macek B, Kumar C, Mortensen P, Mann M (November 2006). "Global, in vivo, and site-specific phosphorylation dynamics in signaling networks". Cell. 127 (3): 635–48. doi:10.1016/j.cell.2006.09.026. PMID 17081983. S2CID 7827573.
Hämäläinen RH, Mowat D, Gabbett MT, O'brien TA, Kallijärvi J, Lehesjoki AE (December 2006). "Wilms' tumor and novel TRIM37 mutations in an Australian patient with mulibrey nanism". Clinical Genetics. 70 (6): 473–9. doi:10.1111/j.1399-0004.2006.00700.x. PMID 17100991. S2CID 20007234.
Doğanc T, Yüksel Konuk BE, Alpan N, Konuk O, Hämäläinen RH, Lehesjoki AE, Tekin M (July 2007). "A novel mutation in TRIM37 is associated with mulibrey nanism in a Turkish boy". Clinical Dysmorphology. 16 (3): 173–6. doi:10.1097/MCD.0b013e3280f6d00b. PMID 17551331. S2CID 45965305.
External links
Overview of all the structural information available in the PDB for UniProt: O94972 (E3 ubiquitin-protein ligase TRIM37) at the PDBe-KB.
