and cell growth. Additionally, eIF3a functions as a translational regulator for several key nucleotide excision repair proteins. Taken together, these properties of eIF3a may explain observations that eIF3a over-expression occurs in 1 eIF3a Regulates NDRG1 during Iron Depletion cancer. Further, eIF3a depletion reduces key malignant attributes such as proliferation, while it increases resistance to treatment with DNA damaging agents. As L-mimosine suppresses global translation as a probable consequence of its iron-chelating activity, the L-mimosinemediated decrease in eIF3a expression is likely to be reflective of the cellular “stress response”. When the latter is activated, global translation is typically suppressed, while certain transcripts encoding key stress-CF-101 site response proteins continue to be translated. While the mechanism by which eIF3a selectively regulates the translation of specific transcripts is unknown, this activity could be a consequence of eIF3a’s role as a constituent of stress granules. Stress granules are cytoplasmic structures that form after exposure to stressors, such as heat shock, oxidative stress, hypoxia etc. They are composed of stalled pre-initiation complexes, small ribosomal subunits and initiation factors . Indeed, the stress granule acts as a “triage center”that sorts, remodels and/or exports specific mRNAs for decay, storage or translation. This process enables translation of only those proteins that are vital for the stress response. Hence, eIF3a may modulate translation of specific transcripts during stress by regulating their distribution between stress granules, polysomes and the sites of mRNA decay. It has been demonstrated that the well characterized metastasis suppressor, N-myc downstream regulated 1 , is upregulated at the levels of both mRNA and protein after treatment with L-mimosine. This suggests that eIF3a may play a role in regulating NDRG1 expression, although this hypothesis has never been examined. Intriguingly, NDRG1 has been identified as a stress-response gene and it was described as a metastasis suppressor in a wide variety of tumors. NDRG1 is also a hypoxia-regulated gene and the hypoxia-inducible factor-1a -dependent up-regulation of NDRG1 transcription has been observed. Further, NDRG1 is markedly induced by iron depletion mediated by the iron chelators, desferrioxamine and 2-hydroxy-1-naphthaldehyde isonicotinoyl hydrazone . Iron chelators mimic hypoxia by inhibiting prolyl hydroxylation and subsequent proteasome-mediated degradation of HIF-1a. Indeed, we showed that regulation of NDRG1 after iron depletion involves HIF-1a-dependent and -independent mechanisms. The current investigation focused on examining the hypothesis that eIF3a contributes to regulating NDRG1 expression during iron depletion. For the first time, this study demonstrates that eIF3a is recruited to stress granules after iron depletion and that eIF3a positively regulates NDRG1 expression under these conditions. The latter event was accompanied by decreased eIF3a expression that occurs during iron depletion and is reflective of the cellular stress 8114006 response. Indeed, the stress response depends on the continued translation of specific stress-response proteins in the face of suppressed global protein 2837278 synthesis. To assess the role of eIF3a in NDRG1 regulation, we implemented eIF3a over-expression and complete ablation models using stably-transfected sense and anti-sense constructs. Notably, eIF3a over-expression poten