Biology:TRIM37
 Generic protein structure example |
Tripartite motif-containing protein 37 is an E3 ubiquitin ligase in humans that is encoded by the TRIM37 gene.[1][2][3][4]
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.[3] It is responsible for the mono-ubiquitination of histone H2A at lysine 119, a modification commonly associated with transcriptional repression.[4][5]
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.[6] 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.[4]
Interactions
TRIM37 has been shown to interact with PRC1.[7] 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.[4] 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.[4]
See also
References
- ↑ "Assignment of the mulibrey nanism gene to 17q by linkage and linkage-disequilibrium analysis". American Journal of Human Genetics 60 (4): 896–902. April 1997. PMID 9106536.
- ↑ "Gene encoding a new RING-B-box-Coiled-coil protein is mutated in mulibrey nanism". Nature Genetics 25 (3): 298–301. July 2000. doi:10.1038/77053. PMID 10888877.
- ↑ 3.0 3.1 "Entrez Gene: TRIM37 tripartite motif-containing 37". https://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=4591.
- ↑ 4.0 4.1 4.2 4.3 4.4 "TRIM37 is a new histone H2A ubiquitin ligase and breast cancer oncoprotein". Nature 516 (7529): 116–20. December 2014. doi:10.1038/nature13955. PMID 25470042. Bibcode: 2014Natur.516..116B.
- ↑ "Histone ubiquitination: triggering gene activity" (in en). Molecular Cell 29 (6): 653–63. March 2008. doi:10.1016/j.molcel.2008.02.014. PMID 18374642.
- ↑ Sinclair, Colleen S.; Rowley, Matthew; Naderi, Ali; Couch, Fergus J. (2003-04-01). "The 17q23 Amplicon and Breast Cancer" (in en). Breast Cancer Research and Treatment 78 (3): 313–322. doi:10.1023/A:1023081624133. ISSN 1573-7217. PMID 12755490.
- ↑ "Towards a proteome-scale map of the human protein-protein interaction network". Nature 437 (7062): 1173–8. October 2005. doi:10.1038/nature04209. PMID 16189514. Bibcode: 2005Natur.437.1173R.
Further reading
- "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. December 1998. doi:10.1093/dnares/5.6.355. PMID 10048485.
- "A diverse family of proteins containing tumor necrosis factor receptor-associated factor domains". The Journal of Biological Chemistry 276 (26): 24242–52. June 2001. doi:10.1074/jbc.M100354200. PMID 11279055.
- "The tripartite motif family identifies cell compartments". The EMBO Journal 20 (9): 2140–51. May 2001. doi:10.1093/emboj/20.9.2140. PMID 11331580.
- "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. October 2001. doi:10.1016/S0925-4773(01)00491-9. PMID 11578880.
- "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. May 2002. doi:10.1086/340256. PMID 11938494.
- "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. June 2003. doi:10.1002/humu.10220. PMID 12754710.
- "Novel mutations in the TRIM37 gene in Mulibrey Nanism". Human Mutation 23 (5): 522. May 2004. doi:10.1002/humu.9233. PMID 15108285.
- "TRIM37 defective in mulibrey nanism is a novel RING finger ubiquitin E3 ligase". Experimental Cell Research 308 (1): 146–55. August 2005. doi:10.1016/j.yexcr.2005.04.001. PMID 15885686.
- "Towards a proteome-scale map of the human protein-protein interaction network". Nature 437 (7062): 1173–8. October 2005. doi:10.1038/nature04209. PMID 16189514. Bibcode: 2005Natur.437.1173R.
- "Insulin resistance syndrome in subjects with mutated RING finger protein TRIM37". Diabetes 54 (12): 3577–81. December 2005. doi:10.2337/diabetes.54.12.3577. PMID 16306379.
- "Characterisation of the mulibrey nanism-associated TRIM37 gene: transcription initiation, promoter region and alternative splicing". Gene 366 (1): 180–8. January 2006. doi:10.1016/j.gene.2005.08.008. PMID 16310976.
- "A protein-protein interaction network for human inherited ataxias and disorders of Purkinje cell degeneration". Cell 125 (4): 801–14. May 2006. doi:10.1016/j.cell.2006.03.032. PMID 16713569.
- "Global, in vivo, and site-specific phosphorylation dynamics in signaling networks". Cell 127 (3): 635–48. November 2006. doi:10.1016/j.cell.2006.09.026. PMID 17081983.
- "Wilms' tumor and novel TRIM37 mutations in an Australian patient with mulibrey nanism". Clinical Genetics 70 (6): 473–9. December 2006. doi:10.1111/j.1399-0004.2006.00700.x. PMID 17100991.
- "A novel mutation in TRIM37 is associated with mulibrey nanism in a Turkish boy". Clinical Dysmorphology 16 (3): 173–6. July 2007. doi:10.1097/MCD.0b013e3280f6d00b. PMID 17551331.
External links
- Overview of all the structural information available in the PDB for UniProt: O94972 (E3 ubiquitin-protein ligase TRIM37) at the PDBe-KB.
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