AP5M1

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AP5M1
Identifiers
AliasesAP5M1, C14orf108, MUDENG, Mu5, MuD, adaptor related protein complex 5 mu 1 subunit, adaptor related protein complex 5 subunit mu 1
External IDsOMIM: 614368 MGI: 1921635 HomoloGene: 10081 GeneCards: AP5M1
Orthologs
SpeciesHumanMouse
Entrez

55745

74385

Ensembl

ENSG00000053770

n/a

UniProt

Q9H0R1

Q8BJ63

RefSeq (mRNA)

NM_018229

NM_144535
NM_001360070

RefSeq (protein)

NP_060699

NP_653118
NP_001346999

Location (UCSC)Chr 14: 57.27 – 57.3 Mbn/a
PubMed search[2][3]
Wikidata
View/Edit HumanView/Edit Mouse
The 3D structure of the protein AP5M1. The alpha fold structure was obtained from Uniprot (AF-Q9H0R1-F1) and modeled using ChimeraX. The three domains are emphasized with color. The first domain is yellow, the second domain is teal, and the third domain is pink.

AP-5 complex subunit mu (AP5M1), otherwise known as MUDENG (MuD), is a protein that is encoded by the AP5M1 gene.[4] The AP5M1 gene was originally discovered when screening for genes which helped to promote death in Fas-mediated apoptosis.[5][6] It is a highly conserved gene.[5][7][6]

MuD is the medium-sized subunit of the AP5 adaptor complex.[8] MuD is expressed throughout the body and is located within both the mitochondria as well as the endoplasmic reticulum (ER) of cells.[5][7][6]

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).[5][7][6][9][10]

Structure[edit]

MuD consists of 490 amino acids that interact to form a tertiary structure with three domains.[11][12]

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.[13][14]

Within the adaptin domain are two aspartic acids, D276 and D290, which serve as binding sites for caspase-3.[14]

Function[edit]

The overall function of MuD remains unclear.[15] It is known, however, that MuD regulates the expression of BAX, a pro-apoptotic member of the Bcl-2 family of proteins.[16][15] Due to— and dependent upon— this relationship, MuD has been able to induce cell death in tumor cells.[17][16][15]

Additionally, MuD has been suggested to be involved in endosomal trafficking.[17][16][18][15]

TRAIL and MuD[edit]

TRAIL, 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.[19][20][21][22] 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.[20][19][21] Tumor cells being treated with TRAIL are 32% more likely to survive when MuD is being expressed.[19]   

References[edit]

  1. ^ a b c GRCh38: Ensembl release 89: ENSG00000053770 – Ensembl, May 2017
  2. ^ "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  3. ^ "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  4. ^ 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.
  5. ^ a b c d 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.
  6. ^ a b c d 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. doi:10.1038/oncsis.2016.30. ISSN 2157-9024. PMC 4945747. PMID 27136675.
  7. ^ a b c 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.
  8. ^ 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.
  9. ^ 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.
  10. ^ 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. S2CID 201095590.
  11. ^ 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.
  12. ^ 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. doi:10.1038/oncsis.2016.30. ISSN 2157-9024. PMC 4945747. PMID 27136675.
  13. ^ 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.
  14. ^ a b 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.
  15. ^ a b c d 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. S2CID 201095590.
  16. ^ a b c 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.
  17. ^ a b 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.
  18. ^ 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.
  19. ^ a b c 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. doi:10.1038/oncsis.2016.30. ISSN 2157-9024. PMC 4945747. PMID 27136675.
  20. ^ a b 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.
  21. ^ a b 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.
  22. ^ 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.


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