TY - JOUR
T1 - Proteome analysis reveals new mechanisms of bcl11b-loss driven apoptosis
AU - Karanam, Narasimha Kumar
AU - Grabarczyk, Piotr
AU - Hammer, Elke
AU - Scharf, Christian
AU - Venz, Simone
AU - Gesell-Salazar, Manuela
AU - Barthlen, Winfried
AU - Przybylski, Grzegorz K.
AU - Schmidt, Christian A.
AU - Völker, Uwe
PY - 2010/8/6
Y1 - 2010/8/6
N2 - 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.
AB - 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.
KW - 2D-DIGE
KW - Bcl11b
KW - ERM (Ezrin
KW - Moesin)
KW - Radixin
KW - cell cycle disturbances
KW - cell death
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U2 - 10.1021/pr901096u
DO - 10.1021/pr901096u
M3 - Article
C2 - 20513151
AN - SCOPUS:77955436918
SN - 1535-3893
VL - 9
SP - 3799
EP - 3811
JO - Journal of Proteome Research
JF - Journal of Proteome Research
IS - 8
ER -