Survivin acetylation linked to STAT3 inhibition

STAT3 and Survivin antibodies are widely used in apoptosis and cancer research studies. Both proteins are known to inhibit apoptosis and are expressed in a number of cancers. In 2006, Gritsko et al suggested STAT3 regulated Survivin expression in tumour cells. Now, a new study by Browns University scientists suggests a role for acetylated Survivin in repressing STAT activity.

STAT3 is a transcription factor which regulates expression of a number of genes, playing a key role in cellular processes such as cell growth and apoptosis. STAT3 is known to play an anti-apoptotic and proliferative role, and its expression is linked to a number of cancers. Although there are no known natural STAT3 mutations, it can nonetheless promote tumour growth by its interaction with other proteins. A study in 2008 showed STAT3 also played a tumour suppressor role in the PTEN pathway.

Survivin is an IAP (inhibitor of apoptosis) protein that is highly expressed in chemoresistant tumours. It regulates cell division and, in combination with other IAPs, plays a role in cytoprotection when the cell is under stress. Antibody studies have shown Survivin interaction with other proteins is dependent upon localization to distinct subcellular compartments, “shuttling” between the cytoplasm and nucleus via NES (nuclear export signalling) pathways. However, the mechanism for this remains unclear.

New evidence from Wang et al, of Brown University suggests nuclear accumulation of Survivin is achieved by acetylation at the lysine 129 position, instigated by CBP (CREB binding protein). This results in Survivin homodimerization and localization to the nucleus. Deacetylation promotes heterodimerisation with CRM1 and export from the nucleus.

Antibody analysis suggested acetylated survivin bound to STAT3 via the transcriptional activation domain, inhibiting activation of STAT3 target genes. PCR and DNA sequencing of a neuroblastoma cell line revealed a mutation at the129K nucleotide caused a defect in survivin nuclear localization, allowing STAT3 transactivation to progress.

The results indicate that acetylation/deacetylation of survivin can affect the ability of STAT3 to activate tumour-causing proteins, suggesting a possible route for therapies against STAT3-dependent tumours. We at Novus Biologicals recently added Survivin [acetyl K129] antibody, used in the study, to our antibody catalog.

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