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The gene encoding GRAMD4 (GRAM domain-containing protein 4) maps to human chromosome 22, which houses over 500 genes and is the second smallest human chromosome. GRAMD4, also designated death-inducing protein (DIP), is a 578 amino acid mitochondrial membrane protein that acts as an essential mediator of the p53-independent E2F-1 death pathway, which is frequently found to be deregulated in several types of cancers. Overexpression of GRAMD4 results in a strong apoptotic response involving caspase-3 activation and cleavage of poly(ADP-ribose)-polymerase. GRAMD4 is expressed in lung and in primary lung squamous cell carcinoma (LSCC) and shows upregulation in mitochondria by E2F1 after addition of 4-hydroxytamoxifen. This evidence suggests that GRAMD4 may be a potential target for cancer therapies.
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