Proteome analysis reveals new mechanisms of bcl11b-loss driven apoptosis

Narasimha Kumar Karanam, Piotr Grabarczyk, Elke Hammer, Christian Scharf, Simone Venz, Manuela Gesell-Salazar, Winfried Barthlen, Grzegorz K. Przybylski, Christian A. Schmidt, Uwe Völker

Research output: Contribution to journalArticle

11 Scopus citations

Abstract

The Bcl11b protein was shown to be important for a variety of functions such as T cell differentiation, normal development of central nervous system, and DNA damage response. Malignant T cells undergo apoptotic cell death upon BCL11B down-regulation, however, the detailed mechanism of cell death is not fully understood yet. Here we employed two-dimensional difference in-gel electrophoresis (2D-DIGE), mass spectrometry and cell biological experiments to investigate the role of Bcl11b in malignant T cell lines such as Jurkat and huT78. We provide evidence for the involvement of the mitochondrial apoptotic pathway and observed cleavage and fragments of known caspase targets such as myosin, spectrin, and vimentin. Our findings suggest an involvement of ERM proteins, which were up-regulated and phosphorylated upon Bcl11b down-regulation. Moreover, the levels of several proteins implicated in cell cycle entry, including DUT-N, CDK6, MCM4, MCM6, and MAT1 were elevated. Thus, the proteome data presented here confirm previous findings concerning the consequences of BCL11B knock-down and provide new insight into the mechanisms of cell death and cell cycle disturbances induced by Bcl11b depletion.

Original languageEnglish (US)
Pages (from-to)3799-3811
Number of pages13
JournalJournal of Proteome Research
Volume9
Issue number8
DOIs
Publication statusPublished - Aug 6 2010
Externally publishedYes

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Keywords

  • 2D-DIGE
  • Bcl11b
  • cell cycle disturbances
  • cell death
  • ERM (Ezrin
  • Moesin)
  • Radixin

ASJC Scopus subject areas

  • Biochemistry
  • Chemistry(all)

Cite this

Karanam, N. K., Grabarczyk, P., Hammer, E., Scharf, C., Venz, S., Gesell-Salazar, M., ... Völker, U. (2010). Proteome analysis reveals new mechanisms of bcl11b-loss driven apoptosis. Journal of Proteome Research, 9(8), 3799-3811. https://doi.org/10.1021/pr901096u