AP5M1

Last updated
AP5M1
Identifiers
Aliases AP5M1 , C14orf108, MUDENG, Mu5, MuD, adaptor related protein complex 5 mu 1 subunit, adaptor related protein complex 5 subunit mu 1
External IDs OMIM: 614368; MGI: 1921635; HomoloGene: 10081; GeneCards: AP5M1; OMA:AP5M1 - orthologs
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 Mb n/a
PubMed search [2] [3]
Wikidata
View/Edit Human View/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. AP5M1 3D Protein Structure.png
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]

Contents

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

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

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

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

  1. 1 2 3 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. 1 2 3 4 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. 1 2 3 4 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. 1 2 3 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. 1 2 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. 1 2 3 4 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. 1 2 3 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. 1 2 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. 1 2 3 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. 1 2 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. 1 2 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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