 | This is the sandbox page where you will draft your initial Wikipedia contribution.
If you're starting a new article, you can develop it here until it's ready to go live. If you're working on improvements to an existing article, copy only one section at a time of the article to this sandbox to work on, and be sure to use an edit summary linking to the article you copied from. Do not copy over the entire article. You can find additional instructions here. Remember to save your work regularly using the "Publish page" button. (It just means 'save'; it will still be in the sandbox.) You can add bold formatting to your additions to differentiate them from existing content. |
Article Draft
edit
AP-5 complex subunit mu (AP5M1), otherwise known as MUDENG (MuD), is a protein that is encoded by the AP5M1 gene.[1] The AP5M1 gene was originally discovered when screening for genes which helped to promote death in Fas-mediated apoptosis.[2][3] It is a highly conserved gene.[2][4][3]
MuD is the medium-sized subunit of the AP5 adaptor complex.[5] MuD is expressed throughout the body and is located within both the mitochondria as well as the endoplasmic reticulum (ER) of cells.[2][4][3]
MuD has been shown to have the ability to induce apoptosis; however, there is evidence that it plays an anti-apoptotic role in apoptosis mediated by tumor necrosis factor-related apoptosis-inducing ligand (TRAIL).[2][4][3][6][7]
Structure
editMuD consists of 490 amino acids that interact to form a tertiary structure with three domains.[4][3]
The overall structure shares similarities with adaptor protein (AP) complexes that are related to clathrin-mediated endocytosis; amino acids 197 through 417 are a shared adaptin domain found in AP μ subunits.[2][6]
Within the adaptin domain are two aspartic acids, D276 and D290, which serve as binding sites for caspase-3.[6]
Function
editThe overall function of MuD remains unclear.[7] It is known, however, that MuD regulates the expression of BAX, a pro-apoptotic member of the Bcl-2 family of proteins.[4][7] Due to— and dependent upon— this relationship, MuD has been able to induce cell death in tumor cells.[2][4][7]
Additionally, MuD has been suggested to be involved in endosomal trafficking.[2][4][5][7]
TRAIL and MuD
editTRAIL, an apoptosis-inducing ligand, activates caspase-8 and caspase-3, which initiate the intrinsic pathway of apoptosis by cleaving BH3 interacting-domain death agonist (Bid) into tBID, another pro-apoptotic member of the Bl-2 protein family.[3][4][6][8] MuD interferes with this process because D276 and D290 act as alternative binding sites for caspase-3, decreasing the amount of BID that gets cleaved.[4][3][6] Tumor cells being treated with TRAIL are 32% more likely to survive when MuD is being expressed.[3]
References
edit- ^ Hirst, Jennifer; Barlow, Lael D.; Francisco, Gabriel Casey; Sahlender, Daniela A.; Seaman, Matthew N. J.; Dacks, Joel B.; Robinson, Margaret S. (2011-10-11). "The fifth adaptor protein complex". PLOS Biology. 9 (10): e1001170. doi:10.1371/journal.pbio.1001170. ISSN 1545-7885. PMC 3191125. PMID 22022230.
{{cite journal}}: CS1 maint: unflagged free DOI (link) - ^ a b c d e f g Lee, Mi-Rha; Shin, Jin Na; Moon, Ae Ran; Park, Sun-Young; Hong, Gilsun; Lee, Mi-Ja; Yun, Cheol-Won; Seol, Dai-Wu; Piya, Sujan; Bae, Jeehyeon; Oh, Jae-Wook; Kim, Tae-Hyoung (2008-06-06). "A novel protein, MUDENG, induces cell death in cytotoxic T cells". Biochemical and Biophysical Research Communications. 370 (3): 504–508. doi:10.1016/j.bbrc.2008.03.139. ISSN 1090-2104. PMID 18395520.
- ^ a b c d e f g h Choi, J.-H.; Lim, J.-B.; Wickramanayake, D. D.; Wagley, Y.; Kim, J.; Lee, H.-C.; Seo, H. G.; Kim, T.-H.; Oh, J.-W. (2016). "Characterization of MUDENG, a novel anti-apoptotic protein". Oncogenesis. 5 (5): e221–e221. doi:10.1038/oncsis.2016.30. ISSN 2157-9024.
- ^ a b c d e f g h i Muthu, Manikandan; Chun, Sechul; Gopal, Judy; Park, Gyun-Seok; Nile, Arti; Shin, Jisoo; Shin, Juhyun; Kim, Tae-Hyoung; Oh, Jae-Wook (2020-08-04). "The MUDENG Augmentation: A Genesis in Anti-Cancer Therapy?". International Journal of Molecular Sciences. 21 (15): 5583. doi:10.3390/ijms21155583. ISSN 1422-0067. PMC 7432215. PMID 32759789.
{{cite journal}}: CS1 maint: unflagged free DOI (link) - ^ a b Hirst, Jennifer; Irving, Carol; Borner, Georg H. H. (2012-11-21). "Adaptor protein complexes AP-4 and AP-5: new players in endosomal trafficking and progressive spastic paraplegia". Traffic. 14 (2): 153–164. doi:10.1111/tra.12028. ISSN 1600-0854. PMID 23167973. S2CID 13766991.
- ^ a b c d e Shin, Jin Na; Han, Ji Hye; Kim, Ji-Young; Moon, Ae-Ran; Kim, Ji Eun; Chang, Jeong Hwan; Bae, Jeehyeon; Oh, Jae Wook; Kim, Tae-Hyoung (2013-05-31). "MUDENG is cleaved by caspase-3 during TRAIL-induced cell death". Biochemical and Biophysical Research Communications. 435 (2): 234–238. doi:10.1016/j.bbrc.2013.04.075. ISSN 1090-2104. PMID 23665015.
- ^ a b c d e Won, Miae; Luo, Yongyang; Lee, Dong-Ho; Shin, Eunkyoung; Suh, Dae-Shik; Kim, Tae-Hyoung; Jin, Hanyong; Bae, Jeehyeon (2019-10-15). "BAX is an essential key mediator of AP5M1-induced apoptosis in cervical carcinoma cells". Biochemical and Biophysical Research Communications. 518 (2): 368–373. doi:10.1016/j.bbrc.2019.08.065. ISSN 1090-2104. PMID 31427081.
- ^ Dimberg, L. Y.; Anderson, C. K.; Camidge, R.; Behbakht, K.; Thorburn, A.; Ford, H. L. (2013-03-14). "On the TRAIL to successful cancer therapy? Predicting and counteracting resistance against TRAIL-based therapeutics". Oncogene. 32 (11): 1341–1350. doi:10.1038/onc.2012.164. ISSN 1476-5594. PMC 4502956. PMID 22580613.