Beclin-1-p53 interaction is crucial for cell fate determination in embryonal carcinoma cells

Rakshamani Tripathi, Dipankar Ash, Chandrima Shaha

Research output: Contribution to journalArticlepeer-review

40 Scopus citations


Emerging interest on the interrelationship between the apoptotic and autophagy pathways in the context of cancer chemotherapy is providing exciting discoveries. Complexes formed between molecules from both pathways present potential targets for chemotherapeutics design as disruption of such complexes could alter cell survival. This study demonstrates an important role of Beclin-1 and p53 interaction in cell fate decision of human embryonal carcinoma cells. The findings provide evidence for p53 interaction with Beclin-1 through the BH3 domain of the latter. This interaction facilitated Beclin-1 ubiquitination through lysine 48 linkage, resulting in proteasome-mediated degradation, consequently maintaining a certain constitutive level of Beclin-1. Disruption of Beclin-1-p53 interaction through shRNA-mediated down-regulation of p53 reduced Beclin-1 ubiquitination suggesting requirement of p53 for the process. Reduction of ubiquitination consequently resulted in an increase in Beclin-1 levels with cells showing high autophagic activity. Enforced overexpression of p53 in the p53 down-regulated cells restored ubiquitination of Beclin-1 reducing its level and lowering autophagic activity. The Beclin-1-p53 interaction was also disrupted by exposure to cisplatin-induced stress resulting in higher level of Beclin-1 because of lesser ubiquitination. This higher concentration of Beclin-1 increased autophagy and offered protection to the cells from cisplatin-induced death. Inhibition of autophagy by either pharmacological or genetic means during cisplatin exposure increased apoptotic death in vitro as well as in xenograft tumours grown in vivo confirming the protective nature of autophagy. Therefore, Beclin-1-p53 interaction defines one additional molecular subroutine crucial for cell fate decisions in embryonal carcinoma cells.

Original languageEnglish (US)
Pages (from-to)2275-2286
Number of pages12
JournalJournal of Cellular and Molecular Medicine
Issue number11
StatePublished - Nov 1 2014
Externally publishedYes


  • Apoptosis
  • Autophagy
  • Beclin-1
  • Cisplatin
  • Embryonal carcinoma cells
  • P53

ASJC Scopus subject areas

  • Molecular Medicine
  • Cell Biology


Dive into the research topics of 'Beclin-1-p53 interaction is crucial for cell fate determination in embryonal carcinoma cells'. Together they form a unique fingerprint.

Cite this