Expression of Daxx sensitizes Jurkat T-cells to the apoptosis-inducing effect of chemotherapeutic agents.
BACKGROUND
The role of Daxx, in particular its ability to promote or hinder apoptosis, still remains controversial. In order to elucidate the functional relevance of Daxx in the extrinsic signaling of malignant lymphocytes Jurkat T-cells were stably transfected with a Daxx-expressing vector or with the respective Daxx-negative control vector.


RESULTS
Assessing first the impact of Daxx expression on the rate of proliferation we demonstrate that overexpression of Daxx alone is not sufficient to alter proliferation in neoplastic lymphocytes. Nevertheless, expression of Daxx down-regulates anti-apoptotic Bcl-2 and up-regulates pro-apoptotic BID. In addition, Daxx-overexpressing Jurkat cells exhibit a decreased expression of the pro-caspase-8, -10, -9 and -3 and a concomitant increase of the inhibitors of apoptosis proteins survivin, XIAP, cIAP-1 and -2. We further demonstrate, that upon incubation with various chemotherapeutic agents these Daxx-induced molecular alterations sensitize Jurkat T-cells to the apoptosis-inducing effects of specific chemotherapeutic agents.


CONCLUSIONS
We here outline the molecular changes elicited by Daxx on major components of the apoptotic cascade of malignant lymphocytes and demonstrate the capacity of Daxx to sensitize these cells to the apoptosis-inducing effect of various chemotherapeutic agents.
Boehrer
Simone
S
Department of Internal Medicine III, Hematology and Oncology, Johann Wolfgang Goethe-University Hospital, Theodor-Stern-Kai 7, 60590 Frankfurt am Main, Germany.
Nowak
Daniel
D
Kukoc-Zivojnov
Natasa
N
Hochmuth
Simone
S
Kim
Soo-Zin
SZ
Hoelzer
Dieter
D
Mitrou
Paris S
PS
Weidmann
Eckhart
E
Chow
Kai Uwe
KU
D048868:Adaptor Proteins, Signal Transducing; D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects* / Q000502:physiology*; D002352:Carrier Proteins / Q000096:biosynthesis* / Q000235:genetics / Q000502:physiology*; D056970:Co-Repressor Proteins; D005786:Gene Expression Regulation / Q000187:drug effects / Q000502:physiology; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics / Q000502:physiology*; D019169:Jurkat Cells; D018832:Molecular Chaperones; D009687:Nuclear Proteins / Q000096:biosynthesis* / Q000235:genetics / Q000502:physiology*; D013601:T-Lymphocytes / Q000187:drug effects* / Q000473:pathology*
D048868:Adaptor Proteins, Signal Transducing; D000970:Antineoplastic Agents; D002352:Carrier Proteins; D056970:Co-Repressor Proteins; C106985:DAXX protein, human; D047908:Intracellular Signaling Peptides and Proteins; D018832:Molecular Chaperones; D009687:Nuclear Proteins