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        <datestamp>2026-10-01T17:42:58Z</datestamp>
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          <dc:title>&lt;p&gt;NOXA is a constitutive pro-apoptotic signal in PEL cell lines.&lt;/p&gt;</dc:title>
          <dc:creator>Prasanth Viswanathan (10314782)</dc:creator>
          <dc:creator>Justine R. Bersonda (25157885)</dc:creator>
          <dc:creator>Jackson Gill (25157888)</dc:creator>
          <dc:creator>Alyssandra Navarro (25157891)</dc:creator>
          <dc:creator>Allison C. Farrar (25157894)</dc:creator>
          <dc:creator>Thomas Caldarera (25157897)</dc:creator>
          <dc:creator>Andrew Murphy (341397)</dc:creator>
          <dc:creator>Daniel Dunham (25157900)</dc:creator>
          <dc:creator>Karl W. Boehme (11384016)</dc:creator>
          <dc:creator>Mark Manzano (25157903)</dc:creator>
          <dc:subject>Biochemistry</dc:subject>
          <dc:subject>Cell Biology</dc:subject>
          <dc:subject>Genetics</dc:subject>
          <dc:subject>Molecular Biology</dc:subject>
          <dc:subject>Cancer</dc:subject>
          <dc:subject>Hematology</dc:subject>
          <dc:subject>Infectious Diseases</dc:subject>
          <dc:subject>Virology</dc:subject>
          <dc:subject>systems biology approach</dc:subject>
          <dc:subject>regulating mitochondrial homeostasis</dc:subject>
          <dc:subject>primary effusion lymphoma</dc:subject>
          <dc:subject>immunoprecipitation experiments show</dc:subject>
          <dc:subject>endogenous reciprocal co</dc:subject>
          <dc:subject>emerging clinical relevance</dc:subject>
          <dc:subject>cell viability due</dc:subject>
          <dc:subject>newly appreciated interaction</dc:subject>
          <dc:subject>causes several malignancies</dc:subject>
          <dc:subject>unexpected genetic interaction</dc:subject>
          <dc:subject>findings thus provide</dc:subject>
          <dc:subject>div &gt;&lt; p</dc:subject>
          <dc:subject>marchf5 oncogenes may</dc:subject>
          <dc:subject>pel cells suggesting</dc:subject>
          <dc:subject>mcl1 motivated us</dc:subject>
          <dc:subject>genetic interaction</dc:subject>
          <dc:subject>tumor cells</dc:subject>
          <dc:subject>causes resistance</dc:subject>
          <dc:subject>thus investigated</dc:subject>
          <dc:subject>therapeutic potential</dc:subject>
          <dc:subject>survival role</dc:subject>
          <dc:subject>significant increase</dc:subject>
          <dc:subject>protein complex</dc:subject>
          <dc:subject>previously shown</dc:subject>
          <dc:subject>pel ).</dc:subject>
          <dc:subject>mechanistic link</dc:subject>
          <dc:subject>kaposi ’</dc:subject>
          <dc:subject>fitness advantage</dc:subject>
          <dc:subject>e3 ligase</dc:subject>
          <dc:subject>drug development</dc:subject>
          <dc:subject>dimerization activities</dc:subject>
          <dc:subject>crispr knockout</dc:subject>
          <dc:subject>combination therapies</dc:subject>
          <dc:subject>chemotherapy regimens</dc:subject>
          <dc:subject>attractive target</dc:subject>
          <dc:subject>associated herpesvirus</dc:subject>
          <dc:subject>apoptotic signal</dc:subject>
          <dc:subject>apoptotic activities</dc:subject>
          <dc:subject>antiviral signaling</dc:subject>
          <dc:description>&lt;p&gt;A. Model to link the oncogenic functions of MARCHF5 and MCL1. We propose that in PEL cell lines, MARCHF5 cooperates with MCL1 function to induce the proteasomal turnover of the MCL1 antagonist NOXA. B. mRNA expression of BH3-only proteins in PEL cell lines from Cell Model Passports. C. Western blots of BH3-only proteins that were targeted for Cas9 KO in BC-3 cells. D. Experimental flow chart of the Fitness Competition Assay. BC-3 Cas9 cells were transduced with a lentivirus encoding the control g&lt;i&gt;AAVS1&lt;/i&gt; and an iRFP670 fluorescent protein or a second lentivirus encoding the targeting gRNA and an eGFP reporter. Equal amounts of control iRFP670 cells were mixed with targeted eGFP cells at the beginning of the growth curve. Fitness indices as reflected by the ratio of eGFP to iRFP670 (eGFP:iRFP670) were measured over 15 days by flow cytometry. E. Fitness indices for each BH3-only KO competition relative to day 0. Statistical differences were calculated using two-way ANOVA with Dunnett’s multiple comparison post-hoc test (n = 3). Adjusted &lt;i&gt;p&lt;/i&gt; values reflect post-hoc comparisons between gSAFE4501 to BH3-only protein gRNA. Error bars, standard error of the mean.&lt;/p&gt;</dc:description>
          <dc:date>2026-10-01T17:54:28Z</dc:date>
          <dc:type>Image</dc:type>
          <dc:type>Figure</dc:type>
          <dc:identifier>10.1371/journal.ppat.1014665.g006</dc:identifier>
          <dc:relation>https://figshare.com/articles/figure/_p_NOXA_is_a_constitutive_pro-apoptotic_signal_in_PEL_cell_lines_p_/34049132</dc:relation>
          <dc:rights>CC BY 4.0</dc:rights>
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