Title : Golgi-SNARE GS28 potentiates cisplatin-induced apoptosis by forming GS28-MDM2-p53 complexes and by preventing the ubiquitination and degradation of p53.

Pub. Date : 2012 Jun 1

PMID : 22397410






9 Functional Relationships(s)
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Protein Name
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1 Golgi-SNARE GS28 potentiates cisplatin-induced apoptosis by forming GS28-MDM2-p53 complexes and by preventing the ubiquitination and degradation of p53. Cisplatin golgi SNAP receptor complex member 1 Homo sapiens
2 Golgi-SNARE GS28 potentiates cisplatin-induced apoptosis by forming GS28-MDM2-p53 complexes and by preventing the ubiquitination and degradation of p53. Cisplatin golgi SNAP receptor complex member 1 Homo sapiens
3 In the present study, we observed that the Golgi-SNARE (soluble N-ethylmaleimide-sensitive fusion protein-attachment protein receptor) GS28 forms a complex with p53 in HEK (human embryonic kidney)-293 cells. Ethylmaleimide golgi SNAP receptor complex member 1 Homo sapiens
4 Given that p53 represents a tumour suppressor that affects the sensitivity of cancer cells to various chemotherapeutic drugs, we examined whether GS28 may influence the level of sensitivity to the DNA-damaging drug cisplatin. Cisplatin golgi SNAP receptor complex member 1 Homo sapiens
5 Indeed, knockdown of GS28 using short-hairpin RNA (shGS28) induced resistance to cisplatin in HEK-293 cells. Cisplatin golgi SNAP receptor complex member 1 Homo sapiens
6 On the other hand, overexpression of GS28 sensitized HEK-293 cells to cisplatin, whereas no sensitization effect was noted for the mitotic spindle-damaging drugs vincristine and taxol. Cisplatin golgi SNAP receptor complex member 1 Homo sapiens
7 Conversely, GS28 overexpression induced the accumulation of p53 and Bax as well as the pro-apoptotic phosphorylation of p53 on Ser(46). Serine golgi SNAP receptor complex member 1 Homo sapiens
8 The modulatory effects of GS28 on cisplatin sensitivity and p53 stability were absent in lung cancer H1299 cells which are p53-null. Cisplatin golgi SNAP receptor complex member 1 Homo sapiens
9 As expected, ectopic expression of p53 in H1299 cells restored the modulatory effects of GS28 on sensitivity to cisplatin. Cisplatin golgi SNAP receptor complex member 1 Homo sapiens