DAP3
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28S ribosomal protein S29, mitochondrial, also known as death-associated protein 3 (DAP3), is a
mitoribosome) and plays key roles in translation, cellular respiration, and apoptosis.[7][8][9][10] Moreover, DAP3 is associated with cancer development, but has been observed to aid some cancers while suppressing others.[10][11][12]
Structure
The DAP3 gene encodes a 46 kDa protein located in the lower area of the small mitoribosomal subunit.
Several splice variants were observed in human ESTs that differ largely in the 5’ UTR region.[7][14] Pseudogenes for this gene are also found in chromosomes 1 and 2.[7]
Function
DAP3 is a 28S subunit protein of mitoribosomes and
Clinical significance
As aforementioned, death associated protein 3 (DAP3) has regulatory roles in
cell respiration and apoptosis. Both opposites and cell respiration are important elements of cell death pathways and have underlying mechanistic roles in ischemia-reperfusion injury.[15][16][17]
During a normal
embryonal
development as programmed cell death and accompanies a variety of normal involutional processes in which it serves as a mechanism to remove "unwanted" cells.
DAP3 has been implicated in numerous cancers. Studies demonstrated that DAP3 expression tended to be low to nonexistent in the tumor cells of
hypermethylation of the gene's promoter.[11][12] Moreover, DAP3 expression has been positively correlated with improved cancer prognosis, indicating that the protein combats cancer progression through its proapoptotic function.[11][12] As a result, DAP3 could serve as a potential biomarker to monitor the effectiveness of therapeutic treatments such as chemotherapy.[11]
However, in other cancers, such as glioblastoma multiforme (GBM) and thymoma, DAP3 expression was found to be upregulated.[10][14] Thus, the specific role of DAP3 in various cancers requires further study.[17]
Interactions
DAP3 has been shown to
interact
with:
- DELE,[12]
- IPS-1,[12]
- AKT,[12]
- PKA,[14]
- PKC,[14]
- NOA1,[8][14]
- FADD,[19]
- Glucocorticoid receptor,[20]
- Heat shock protein 90kDa alpha (cytosolic), member A1,[20] and
- TNFRSF10A.[19]
References
- ^ a b c GRCh38: Ensembl release 89: ENSG00000132676 – Ensembl, May 2017
- ^ a b c GRCm38: Ensembl release 89: ENSMUSG00000068921 – 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.
- PMID 7499268.
- PMID 9284927.
- ^ a b c d e f g "Entrez Gene: DAP3 death associated protein 3".
- ^ PMID 19103604.
- ^ PMID 18227431.
- ^ PMID 19536094.
- ^ PMID 24300973.
- ^ PMID 22287761.
- ^ PMID 15302871.
- ^ PMID 20079882.
- PMID 26014222.
- PMID 16219456.
- ^ PMID 9679246.
- PMID 4561027.
- ^ S2CID 6923467.
- ^ PMID 10903152.
Further reading
- Maruyama K, Sugano S (1994). "Oligo-capping: a simple method to replace the cap structure of eukaryotic mRNAs with oligoribonucleotides". Gene. 138 (1–2): 171–4. PMID 8125298.
- Suzuki Y, Yoshitomo-Nakagawa K, Maruyama K, Suyama A, Sugano S (1997). "Construction and characterization of a full length-enriched and a 5'-end-enriched cDNA library". Gene. 200 (1–2): 149–56. PMID 9373149.
- Hulkko SM, Wakui H, Zilliacus J (2000). "The pro-apoptotic protein death-associated protein 3 (DAP3) interacts with the glucocorticoid receptor and affects the receptor function". Biochem. J. 349 (Pt 3): 885–93. PMID 10903152.
- Morgan CJ, Jacques C, Savagner F, Tourmen Y, Mirebeau DP, Malthièry Y, Reynier P (2001). "A conserved N-terminal sequence targets human DAP3 to mitochondria". Biochem. Biophys. Res. Commun. 280 (1): 177–81. PMID 11162496.
- Cavdar Koc E, Ranasinghe A, Burkhart W, Blackburn K, Koc H, Moseley A, Spremulli LL (2001). "A new face on apoptosis: death-associated protein 3 and PDCD9 are mitochondrial ribosomal proteins". FEBS Lett. 492 (1–2): 166–70. PMID 11248257.
- Cavdar Koc E, Burkhart W, Blackburn K, Moseley A, Spremulli LL (2001). "The small subunit of the mammalian mitochondrial ribosome. Identification of the full complement of ribosomal proteins present". J. Biol. Chem. 276 (22): 19363–74. PMID 11279123.
- Miyazaki T, Reed JC (2001). "A GTP-binding adapter protein couples TRAIL receptors to apoptosis-inducing proteins". Nat. Immunol. 2 (6): 493–500. S2CID 6923467.
- Suzuki T, Terasaki M, Takemoto-Hori C, Hanada T, Ueda T, Wada A, Watanabe K (2001). "Proteomic analysis of the mammalian mitochondrial ribosome. Identification of protein components in the 28 S small subunit". J. Biol. Chem. 276 (35): 33181–95. PMID 11402041.
- Kenmochi N, Suzuki T, Uechi T, Magoori M, Kuniba M, Higa S, Watanabe K, Tanaka T (2001). "The human mitochondrial ribosomal protein genes: mapping of 54 genes to the chromosomes and implications for human disorders". Genomics. 77 (1–2): 65–70. PMID 11543634.
- Berger T, Kretzler M (2002). "Interaction of DAP3 and FADD only after cellular disruption". Nat. Immunol. 3 (1): 3–5. S2CID 35379239.
- Hulkko SM, Zilliacus J (2002). "Functional interaction between the pro-apoptotic DAP3 and the glucocorticoid receptor". Biochem. Biophys. Res. Commun. 295 (3): 749–55. PMID 12099703.
- Berger T, Kretzler M (2002). "TRAIL-induced apoptosis is independent of the mitochondrial apoptosis mediator DAP3". Biochem. Biophys. Res. Commun. 297 (4): 880–4. PMID 12359235.
- Zhang Z, Gerstein M (2003). "Identification and characterization of over 100 mitochondrial ribosomal protein pseudogenes in the human genome". Genomics. 81 (5): 468–80. PMID 12706105.
- Mukamel Z, Kimchi A (2004). "Death-associated protein 3 localizes to the mitochondria and is involved in the process of mitochondrial fragmentation during cell death". J. Biol. Chem. 279 (35): 36732–8. PMID 15175341.
- Hirota T, Obara K, Matsuda A, Akahoshi M, Nakashima K, Hasegawa K, Takahashi N, Shimizu M, Sekiguchi H, Kokubo M, Doi S, Fujiwara H, Miyatake A, Fujita K, Enomoto T, Kishi F, Suzuki Y, Saito H, Nakamura Y, Shirakawa T, Tamari M (2004). "Association between genetic variation in the gene for death-associated protein-3 (DAP3) and adult asthma". J. Hum. Genet. 49 (7): 370–5. PMID 15179560.
- Miyazaki T, Shen M, Fujikura D, Tosa N, Kim HR, Kon S, Uede T, Reed JC (2004). "Functional role of death-associated protein 3 (DAP3) in anoikis". J. Biol. Chem. 279 (43): 44667–72. PMID 15302871.
- Sasaki H, Ide N, Yukiue H, Kobayashi Y, Fukai I, Yamakawa Y, Fujii Y (2004). "Arg and DAP3 expression was correlated with human thymoma stage". Clin. Exp. Metastasis. 21 (6): 507–13. S2CID 23560519.
External links
- PDBe-KB provides an overview of all the structure information available in the PDB for Human 28S ribosomal protein S29, mitochondrial (DAP3)