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AIFM2
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<h2 id="function">Function</h2> <p>The AIFM2 gene encodes the FSP1 protein encoded by this gene has significant <a href="/facts/Homology_(biology)/muctKlyT">homology</a> to <a href="/facts/NADH/BHdLW925">NADH</a> <a href="/facts/Oxidoreductase/neW0G5D4">oxidoreductases</a> and the <a href="/facts/Apoptosis-inducing_factor/GtNk2KfX">apoptosis-inducing factor</a> PDCD8/<a href="/facts/Apoptosis-inducing_factor/GtNk2KfX">AIF</a>. Although it was originally proposed that this protein induce <a href="/facts/Apoptosis/8dVzSm4y">apoptosis</a> due to its similarity with AIF, findings from James Olzmann's group at UC Berkeley <a class="footnote-ref" id="fnref:7" href="#fn:7"><sup>7</sup></a> and Marcus Conrad's group at the Helmholtz Institute <a class="footnote-ref" id="fnref:8" href="#fn:8"><sup>8</sup></a> demonstrated that the primary cellular function of FSP1 is to suppress lipid peroxidation and the induction of the regulated, non-apoptotic cell death pathway known as <a href="/facts/Ferroptosis/wL53toRk">ferroptosis</a>. Mechanistically, FSP1 reduces oxidized coenzyme Q10 (i.e., ubiquinone) to its reduced form (i.e., ubiquinol), which functions as an excellent lipophilic antioxidant to prevent the propagation of lipid peroxidation.<a class="footnote-ref" id="fnref:9" href="#fn:9"><sup>9</sup></a><a class="footnote-ref" id="fnref:10" href="#fn:10"><sup>10</sup></a> FSP1 also may act through the reduction of other molecules, such as vitamin E and vitamin K. </p> <h2 id="structure">Structure</h2> <p>AIFM2 can be found only both in <a href="/facts/Prokaryote/oYyvaDDH">prokaryotes</a> and eukaryotes.<a class="footnote-ref" id="fnref:11" href="#fn:11"><sup>11</sup></a><a class="footnote-ref" id="fnref:12" href="#fn:12"><sup>12</sup></a><a class="footnote-ref" id="fnref:13" href="#fn:13"><sup>13</sup></a><a class="footnote-ref" id="fnref:14" href="#fn:14"><sup>14</sup></a> Sequence analysis reveals that the <i>AIFM2</i> <a href="/facts/Gene_promoter/YDYBzLfg">gene promoter</a> contains a consensus <a href="/facts/Transcription_(genetics)/bDgp9HDN">transcription</a> initiator sequence instead of a <a href="/facts/TATA_box/GFu8tHxH">TATA box</a>.<a class="footnote-ref" id="fnref:15" href="#fn:15"><sup>15</sup></a> Though AIFM2 also lacks a recognizable <a href="/facts/Targeting_sequence/9oARjq52">mitochondrial localization sequence</a> and cannot enter the mitochondria, it is found to adhere to the <a href="/facts/Outer_mitochondrial_membrane/ErHqrdJ1">outer mitochondrial membrane</a> (OMM), where it forms a ring-like structure.<a class="footnote-ref" id="fnref:16" href="#fn:16"><sup>16</sup></a><a class="footnote-ref" id="fnref:17" href="#fn:17"><sup>17</sup></a><a class="footnote-ref" id="fnref:18" href="#fn:18"><sup>18</sup></a><a class="footnote-ref" id="fnref:19" href="#fn:19"><sup>19</sup></a><a class="footnote-ref" id="fnref:20" href="#fn:20"><sup>20</sup></a> Two deletion mutations at the <a href="/facts/N-terminal/yKYpuaBJ">N-terminal</a> (aa 1–185 and 1–300) result in <a href="/facts/Cell_nucleus/D7sFRa3c">nuclear</a> localization and failure to effect cell death, suggesting that AIFM2 must be associated with the mitochondria in order to induce apoptosis. Moreover, domain mapping experiments reveal that only the C-terminal 187 aa is required for apoptotic induction.<a class="footnote-ref" id="fnref:21" href="#fn:21"><sup>21</sup></a> Meanwhile, mutations in the <a href="/facts/N-terminal/yKYpuaBJ">N-terminal</a> putative FAD- and ADP-binding domains, which are responsible for its oxidoreductase function, do not affect its apoptotic function, thus indicating that these two functions operate independently.<a class="footnote-ref" id="fnref:22" href="#fn:22"><sup>22</sup></a><a class="footnote-ref" id="fnref:23" href="#fn:23"><sup>23</sup></a> It assembles stoichiometrically and noncovalently with 6-hydroxy-FAD.<a class="footnote-ref" id="fnref:24" href="#fn:24"><sup>24</sup></a> </p><p>The <i>AIFM2</i> gene contains a putative p53-binding element in <a href="/facts/Intron/LS6YdBEK">intron</a> 5, suggesting that its gene expression can be activated by p53.<a class="footnote-ref" id="fnref:25" href="#fn:25"><sup>25</sup></a><a class="footnote-ref" id="fnref:26" href="#fn:26"><sup>26</sup></a><a class="footnote-ref" id="fnref:27" href="#fn:27"><sup>27</sup></a> </p> <h2 id="function">Function</h2> <p>This protein is a flavoprotein that functions as an NAD(P)H-dependent oxidoreductase and induces <a href="/facts/Caspase/YPl75Q9B">caspase</a>- and <a href="/facts/P53/YEGULLgM">p53</a>-independent apoptosis.<a class="footnote-ref" id="fnref:28" href="#fn:28"><sup>28</sup></a><a class="footnote-ref" id="fnref:29" href="#fn:29"><sup>29</sup></a><a class="footnote-ref" id="fnref:30" href="#fn:30"><sup>30</sup></a> The exact mechanisms remain unknown, but AIFM2 is found to <a href="/facts/Subcellular_localization/50QUENGB">localize</a> to the <a href="/facts/Cytosol/VyXgygWm">cytosol</a> and the OMM. Thus, it may carry out this function by disrupting mitochondrial morphology and releasing proapoptotic factors.<a class="footnote-ref" id="fnref:31" href="#fn:31"><sup>31</sup></a> Also, under conditions of stress which activate p53-mediated apoptosis, such as <a href="/facts/Hypoxia_(medical)/JWV04G89">hypoxia</a>, AIMF2 may stabilize <a href="/facts/P53/YEGULLgM">p53</a> by inhibiting its degradation and accelerate the apoptotic process. Under normal conditions (i.e., undetectable p53 expression), the <i>AIFM2</i> gene is highly expressed in the <a href="/facts/Heart/fF4KSGdk">heart</a>, followed by <a href="/facts/Liver/Rtp4Fk2b">liver</a> and <a href="/facts/Skeletal_muscle/en1tVYFN">skeletal muscle</a>, with low levels detected in the <a href="/facts/Placenta/7XUoks1b">placenta</a>, <a href="/facts/Lung/gTWXI6Fj">lung</a>, <a href="/facts/Kidney/HBspPrv9">kidney</a>, and <a href="/facts/Pancreas/r0WPGjAq">pancreas</a> and the lowest in the <a href="/facts/Brain/Xo5ABfXl">brain</a>. However, in organs such as the heart, there may be additional regulatory mechanisms to suppress its proapoptotic function.<a class="footnote-ref" id="fnref:32" href="#fn:32"><sup>32</sup></a> For instance, AIFM2 may be able to directly bind nuclear DNA and effect chromatin condensation, as with AIF.<a class="footnote-ref" id="fnref:33" href="#fn:33"><sup>33</sup></a> Furthermore, AIMF2 expressed at low levels may function as an oxidoreductase involved in metabolism.<a class="footnote-ref" id="fnref:34" href="#fn:34"><sup>34</sup></a> Hence, under normal cellular conditions, AIFM2 may promote cell survival rather than death by metabolic processes such as generating <a href="/facts/Reactive_oxygen_species/GpwSRugH">reactive oxygen species</a> (ROS) to maintain survival signaling.<a class="footnote-ref" id="fnref:35" href="#fn:35"><sup>35</sup></a> </p> <h2 id="clinical-significance">Clinical significance</h2> <p><i>AIFM2</i> has been implicated in <a href="/facts/Tumorigenesis/PC8wc1Mf">tumorigenesis</a> as a p53-inducible gene.<a class="footnote-ref" id="fnref:36" href="#fn:36"><sup>36</sup></a> <i>AIFM2</i> mRNA levels are observed to be downregulated in many human cancer tissues, though a previous study reported that <i>AIFM2</i> mRNA transcripts were only detected in <a href="/facts/Colon_cancer/nV592sW7">colon cancer</a> and <a href="/facts/B-cell_lymphoma/q1m7JHdD">B-cell lymphoma</a> cell lines.<a class="footnote-ref" id="fnref:37" href="#fn:37"><sup>37</sup></a><a class="footnote-ref" id="fnref:38" href="#fn:38"><sup>38</sup></a> Furthermore, its DNA-binding ability contributes to its involvement in the apoptosis-inducing response to viral and bacterial infections, possibly through its role in ROS regulation.<a class="footnote-ref" id="fnref:39" href="#fn:39"><sup>39</sup></a> </p><p>Inhibitors<a class="footnote-ref" id="fnref:40" href="#fn:40"><sup>40</sup></a><a class="footnote-ref" id="fnref:41" href="#fn:41"><sup>41</sup></a> of FSP1 have been identified to induce ferroptosis. icFSP1 has been shown to cause dissociation of FSP1 from the membrane and phase separation of FSP1 into droplets. </p> <h2 id="evolution">Evolution</h2> <p>The phylogenetic studies indicates that the divergence of the AIFM1 and other AIFs occurred before the divergence of eukaryotes.<a class="footnote-ref" id="fnref:42" href="#fn:42"><sup>42</sup></a> </p> <h2 id="interactions">Interactions</h2> <p>AIFM2 is shown to <a href="/facts/Protein_interaction/etvm9Wmg">interact</a> with <a href="/facts/P53/YEGULLgM">p53</a>.<a class="footnote-ref" id="fnref:43" href="#fn:43"><sup>43</sup></a> </p><p>AIFM2 is not inhibited by <a href="/facts/Bcl-2/I34R1guW">Bcl-2</a>.<a class="footnote-ref" id="fnref:44" href="#fn:44"><sup>44</sup></a> </p><p>AIFM2 can also bind the following coenzymes: </p> <ul><li>6-hydroxy-FAD,<a class="footnote-ref" id="fnref:45" href="#fn:45"><sup>45</sup></a></li> <li><a href="/facts/Flavin_adenine_dinucleotide/uzADx3ES">Flavin adenine dinucleotide</a> (FAD),<a class="footnote-ref" id="fnref:46" href="#fn:46"><sup>46</sup></a></li> <li><a href="/facts/NADPH/XMgmPQ5t">NADPH</a>/NADP+,<a class="footnote-ref" id="fnref:47" href="#fn:47"><sup>47</sup></a></li> <li><a href="/facts/NADH/BHdLW925">NADH</a>/NAD+,<a class="footnote-ref" id="fnref:48" href="#fn:48"><sup>48</sup></a> and</li> <li>pyridine nucleotide coenzyme.<a class="footnote-ref" id="fnref:49" href="#fn:49"><sup>49</sup></a></li></ul> <h2 id="further-reading">Further reading</h2> <ul><li>Horikoshi N, Cong J, Kley N, Shenk T (August 1999). "Isolation of differentially expressed cDNAs from p53-dependent apoptotic cells: activation of the human homologue of the Drosophila peroxidasin gene". <i>Biochemical and Biophysical Research Communications</i>. 261 (3): 864–9. <a href="/facts/Bibcode_(identifier)/9HtdQSGB">Bibcode</a>:<a href="https://ui.adsabs.harvard.edu/abs/1999BBRC..261..864H">1999BBRC..261..864H</a>. <a href="/facts/Doi_(identifier)/muM9Etpq">doi</a>:<a href="https://doi.org/10.1006%2Fbbrc.1999.1123">10.1006/bbrc.1999.1123</a>. <a href="/facts/PMID_(identifier)/JlHAvMHt">PMID</a> <a href="https://pubmed.ncbi.nlm.nih.gov/10441517">10441517</a>.</li> <li>Zhang W, Li D, Mehta JL (January 2004). "Role of AIF in human coronary artery endothelial cell apoptosis". <i>American Journal of Physiology. Heart and Circulatory Physiology</i>. 286 (1): H354-8. <a href="/facts/Doi_(identifier)/muM9Etpq">doi</a>:<a href="https://doi.org/10.1152%2Fajpheart.00579.2003">10.1152/ajpheart.00579.2003</a>. <a href="/facts/PMID_(identifier)/JlHAvMHt">PMID</a> <a href="https://pubmed.ncbi.nlm.nih.gov/14684364">14684364</a>.</li> <li>Wu M, Xu LG, Su T, Tian Y, Zhai Z, Shu HB (September 2004). "AMID is a p53-inducible gene downregulated in tumors". <i>Oncogene</i>. 23 (40): 6815–9. <a href="/facts/Doi_(identifier)/muM9Etpq">doi</a>:<a href="https://doi.org/10.1038%2Fsj.onc.1207909">10.1038/sj.onc.1207909</a>. <a href="/facts/PMID_(identifier)/JlHAvMHt">PMID</a> <a href="https://pubmed.ncbi.nlm.nih.gov/15273740">15273740</a>. <a href="/facts/S2CID_(identifier)/ldJsHa2Y">S2CID</a> <a href="https://api.semanticscholar.org/CorpusID:8541615">8541615</a>.</li> <li>Varecha M, Amrichová J, Zimmermann M, Ulman V, Lukásová E, Kozubek M (July 2007). "Bioinformatic and image analyses of the cellular localization of the apoptotic proteins endonuclease G, AIF, and AMID during apoptosis in human cells". <i>Apoptosis</i>. 12 (7): 1155–71. <a href="/facts/Doi_(identifier)/muM9Etpq">doi</a>:<a href="https://doi.org/10.1007%2Fs10495-007-0061-0">10.1007/s10495-007-0061-0</a>. <a href="/facts/PMID_(identifier)/JlHAvMHt">PMID</a> <a href="https://pubmed.ncbi.nlm.nih.gov/17347867">17347867</a>. <a href="/facts/S2CID_(identifier)/ldJsHa2Y">S2CID</a> <a href="https://api.semanticscholar.org/CorpusID:29846503">29846503</a>.</li> <li>Gong M, Hay S, Marshall KR, Munro AW, Scrutton NS (October 2007). <a href="https://doi.org/10.1074%2Fjbc.M703713200">"DNA binding suppresses human AIF-M2 activity and provides a connection between redox chemistry, reactive oxygen species, and apoptosis"</a>. <i>The Journal of Biological Chemistry</i>. 282 (41): 30331–40. <a href="/facts/Doi_(identifier)/muM9Etpq">doi</a>:<a href="https://doi.org/10.1074%2Fjbc.M703713200">10.1074/jbc.M703713200</a>. <a href="/facts/PMID_(identifier)/JlHAvMHt">PMID</a> <a href="https://pubmed.ncbi.nlm.nih.gov/17711848">17711848</a>.</li></ul> <h2 id="external-links">External links</h2> <ul><li>Human <a href="https://genome.ucsc.edu/cgi-bin/hgTracks?db=hg38&singleSearch=knownCanonical&position=AIFM2"><i>AIFM2</i></a> genome location and <a href="https://genome.ucsc.edu/cgi-bin/hgGene?db=hg38&hgg_type=knownGene&hgg_gene=AIFM2"><i>AIFM2</i></a> gene details page in the <a href="/facts/UCSC_Genome_Browser/kwumPyLb">UCSC Genome Browser</a>.</li> <li>Human <a href="https://genome.ucsc.edu/cgi-bin/hgTracks?db=hg38&singleSearch=knownCanonical&position=PRG3"><i>PRG3</i></a> genome location and <a href="https://genome.ucsc.edu/cgi-bin/hgGene?db=hg38&hgg_type=knownGene&hgg_gene=PRG3"><i>PRG3</i></a> gene details page in the <a href="/facts/UCSC_Genome_Browser/kwumPyLb">UCSC Genome Browser</a>.</li></ul> <h2 id="references">References</h2> <ol> <li id="fn:1"><p>Ohiro Y, Garkavtsev I, Kobayashi S, Sreekumar KR, Nantz R, Higashikubo BT, Duffy SL, Higashikubo R, Usheva A, Gius D, Kley N, Horikoshi N (July 2002). "A novel p53-inducible apoptogenic gene, PRG3, encodes a homologue of the apoptosis-inducing factor (AIF)". FEBS Letters. 524 (1–3): 163–71. Bibcode:2002FEBSL.524..163O. doi:10.1016/S0014-5793(02)03049-1. PMID 12135761. S2CID 6972218. <a href="https://doi.org/10.1016%2FS0014-5793%2802%2903049-1" target="_blank">https://doi.org/10.1016%2FS0014-5793%2802%2903049-1</a> <a href="#fnref:1" class="footnote-back-ref">↩</a></p></li> <li id="fn:2"><p>Wu M, Xu LG, Li X, Zhai Z, Shu HB (July 2002). "AMID, an apoptosis-inducing factor-homologous mitochondrion-associated protein, induces caspase-independent apoptosis". The Journal of Biological Chemistry. 277 (28): 25617–23. doi:10.1074/jbc.M202285200. PMID 11980907. <a href="https://doi.org/10.1074%2Fjbc.M202285200" target="_blank">https://doi.org/10.1074%2Fjbc.M202285200</a> <a href="#fnref:2" class="footnote-back-ref">↩</a></p></li> <li id="fn:3"><p>Marshall KR, Gong M, Wodke L, Lamb JH, Jones DJ, Farmer PB, Scrutton NS, Munro AW (September 2005). "The human apoptosis-inducing protein AMID is an oxidoreductase with a modified flavin cofactor and DNA binding activity". The Journal of Biological Chemistry. 280 (35): 30735–40. doi:10.1074/jbc.M414018200. PMID 15958387. <a href="https://doi.org/10.1074%2Fjbc.M414018200" target="_blank">https://doi.org/10.1074%2Fjbc.M414018200</a> <a href="#fnref:3" class="footnote-back-ref">↩</a></p></li> <li id="fn:4"><p>"Entrez Gene: AIFM2 apoptosis-inducing factor, mitochondrion-associated, 2". <a href="https://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=84883" target="_blank">https://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=84883</a> <a href="#fnref:4" class="footnote-back-ref">↩</a></p></li> <li id="fn:5"><p>Doll S, Freitas FP, Shah R, Aldrovandi M, da Silva MC, Ingold I, et al. (November 2019). "FSP1 is a glutathione-independent ferroptosis suppressor". Nature. 575 (7784): 693–698. Bibcode:2019Natur.575..693D. doi:10.1038/s41586-019-1707-0. hdl:10044/1/75345. PMID 31634899. S2CID 204833583. <a href="https://orca.cardiff.ac.uk/id/eprint/126674/" target="_blank">https://orca.cardiff.ac.uk/id/eprint/126674/</a> <a href="#fnref:5" class="footnote-back-ref">↩</a></p></li> <li id="fn:6"><p>Bersuker K, Hendricks JM, Li Z, Magtanong L, Ford B, Tang PH, et al. (November 2019). "The CoQ oxidoreductase FSP1 acts parallel to GPX4 to inhibit ferroptosis". Nature. 575 (7784): 688–692. Bibcode:2019Natur.575..688B. doi:10.1038/s41586-019-1705-2. PMC 6883167. PMID 31634900. <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6883167" target="_blank">https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6883167</a> <a href="#fnref:6" class="footnote-back-ref">↩</a></p></li> <li id="fn:7"><p>Bersuker K, Hendricks JM, Li Z, Magtanong L, Ford B, Tang PH, et al. (November 2019). "The CoQ oxidoreductase FSP1 acts parallel to GPX4 to inhibit ferroptosis". Nature. 575 (7784): 688–692. Bibcode:2019Natur.575..688B. doi:10.1038/s41586-019-1705-2. PMC 6883167. PMID 31634900. <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6883167" target="_blank">https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6883167</a> <a href="#fnref:7" class="footnote-back-ref">↩</a></p></li> <li id="fn:8"><p>Doll S, Freitas FP, Shah R, Aldrovandi M, da Silva MC, Ingold I, et al. (November 2019). "FSP1 is a glutathione-independent ferroptosis suppressor". Nature. 575 (7784): 693–698. Bibcode:2019Natur.575..693D. doi:10.1038/s41586-019-1707-0. hdl:10044/1/75345. PMID 31634899. S2CID 204833583. <a href="https://orca.cardiff.ac.uk/id/eprint/126674/" target="_blank">https://orca.cardiff.ac.uk/id/eprint/126674/</a> <a href="#fnref:8" class="footnote-back-ref">↩</a></p></li> <li id="fn:9"><p>Doll S, Freitas FP, Shah R, Aldrovandi M, da Silva MC, Ingold I, et al. (November 2019). "FSP1 is a glutathione-independent ferroptosis suppressor". Nature. 575 (7784): 693–698. Bibcode:2019Natur.575..693D. doi:10.1038/s41586-019-1707-0. hdl:10044/1/75345. PMID 31634899. S2CID 204833583. <a href="https://orca.cardiff.ac.uk/id/eprint/126674/" target="_blank">https://orca.cardiff.ac.uk/id/eprint/126674/</a> <a href="#fnref:9" class="footnote-back-ref">↩</a></p></li> <li id="fn:10"><p>Bersuker K, Hendricks JM, Li Z, Magtanong L, Ford B, Tang PH, et al. (November 2019). "The CoQ oxidoreductase FSP1 acts parallel to GPX4 to inhibit ferroptosis". Nature. 575 (7784): 688–692. Bibcode:2019Natur.575..688B. doi:10.1038/s41586-019-1705-2. PMC 6883167. PMID 31634900. <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6883167" target="_blank">https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6883167</a> <a href="#fnref:10" class="footnote-back-ref">↩</a></p></li> <li id="fn:11"><p>Wu M, Xu LG, Li X, Zhai Z, Shu HB (July 2002). "AMID, an apoptosis-inducing factor-homologous mitochondrion-associated protein, induces caspase-independent apoptosis". The Journal of Biological Chemistry. 277 (28): 25617–23. doi:10.1074/jbc.M202285200. PMID 11980907. <a href="https://doi.org/10.1074%2Fjbc.M202285200" target="_blank">https://doi.org/10.1074%2Fjbc.M202285200</a> <a href="#fnref:11" class="footnote-back-ref">↩</a></p></li> <li id="fn:12"><p>Marshall KR, Gong M, Wodke L, Lamb JH, Jones DJ, Farmer PB, Scrutton NS, Munro AW (September 2005). "The human apoptosis-inducing protein AMID is an oxidoreductase with a modified flavin cofactor and DNA binding activity". The Journal of Biological Chemistry. 280 (35): 30735–40. doi:10.1074/jbc.M414018200. PMID 15958387. <a href="https://doi.org/10.1074%2Fjbc.M414018200" target="_blank">https://doi.org/10.1074%2Fjbc.M414018200</a> <a href="#fnref:12" class="footnote-back-ref">↩</a></p></li> <li id="fn:13"><p>Klim J, Gładki A, Kucharczyk R, Zielenkiewicz U, Kaczanowski S (May 2018). "Ancestral State Reconstruction of the Apoptosis Machinery in the Common Ancestor of Eukaryotes". G3. 8 (6): 2121–2134. doi:10.1534/g3.118.200295. PMC 5982838. PMID 29703784. <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5982838" target="_blank">https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5982838</a> <a href="#fnref:13" class="footnote-back-ref">↩</a></p></li> <li id="fn:14"><p>Wu M, Xu LG, Su T, Tian Y, Zhai Z, Shu HB (September 2004). "AMID is a p53-inducible gene downregulated in tumors". Oncogene. 23 (40): 6815–9. doi:10.1038/sj.onc.1207909. PMID 15273740. S2CID 8541615. <a href="/wiki/Doi_(identifier)" target="_blank">/wiki/Doi_(identifier)</a> <a href="#fnref:14" class="footnote-back-ref">↩</a></p></li> <li id="fn:15"><p>Wu M, Xu LG, Su T, Tian Y, Zhai Z, Shu HB (September 2004). "AMID is a p53-inducible gene downregulated in tumors". Oncogene. 23 (40): 6815–9. doi:10.1038/sj.onc.1207909. PMID 15273740. S2CID 8541615. <a href="/wiki/Doi_(identifier)" target="_blank">/wiki/Doi_(identifier)</a> <a href="#fnref:15" class="footnote-back-ref">↩</a></p></li> <li id="fn:16"><p>Wu M, Xu LG, Li X, Zhai Z, Shu HB (July 2002). "AMID, an apoptosis-inducing factor-homologous mitochondrion-associated protein, induces caspase-independent apoptosis". The Journal of Biological Chemistry. 277 (28): 25617–23. doi:10.1074/jbc.M202285200. PMID 11980907. <a href="https://doi.org/10.1074%2Fjbc.M202285200" target="_blank">https://doi.org/10.1074%2Fjbc.M202285200</a> <a href="#fnref:16" class="footnote-back-ref">↩</a></p></li> <li id="fn:17"><p>Ohiro Y, Garkavtsev I, Kobayashi S, Sreekumar KR, Nantz R, Higashikubo BT, Duffy SL, Higashikubo R, Usheva A, Gius D, Kley N, Horikoshi N (July 2002). "A novel p53-inducible apoptogenic gene, PRG3, encodes a homologue of the apoptosis-inducing factor (AIF)". FEBS Letters. 524 (1–3): 163–71. Bibcode:2002FEBSL.524..163O. doi:10.1016/S0014-5793(02)03049-1. PMID 12135761. 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