Daxx is required for stress-induced cell death and JNK activation

Abstract

Daxx has been implicated in the modulation of apoptosis in response to various stimuli. In the nucleus, Daxx interacts and colocalizes with the promyelocytic leukemia protein (PML) into the PML-nuclear body. Moreover, overexpressed Daxx positively modulates FAS-ligand and TGFb-induced apoptosis. However, recent reports indicate that Daxx can also act as an antiapoptotic factor. As most studies on the role of Daxx in cell death have been conducted using tumour cell lines, we analysed the function of Daxx in physiological settings. We found that Daxx is induced upon exposure to ultraviolet (UV) irradiation and hydrogen peroxide treatment. We employed RNA interference to downregulate Daxx in primary fibroblasts. Remarkably, Daxx-depleted cells are resistant to cell death induced by both UV irradiation and oxidative stress. Furthermore, the downregulation of Daxx results in impaired MKK/c-Jun-N-terminal kinase (JNK) activation. This is the first evidence that Daxx promotes cell death and JNK activation in physiological conditions.

Wiring the cell signaling circuitry by the NF-κB and JNK1 crosstalk and its applications in human diseases

“…UV elicits cell death through both membrane death receptor-dependent extrinsic death pathway and ROS-dependent intrinsic mitochondria-dependent death pathway (Figure 4). UV rapidly induces robust and sustained JNK through the cytoplasmic membrane receptors such as tyrosine kinase receptors and TNF-R1 (Rosette and Karin, 1996), as well as DNA damage (Lee et al, 1998;Khelifi et al, 2005). Recent studies show that JNK1, but not JNK2 is essential for UV-induced cell death (Liu et al, , 2006.…”

Acetylcholinesterase expression mediated by c-Jun-NH2-terminal kinase pathway during anticancer drug-induced apoptosis

“…c-Jun NH2-terminal kinases (JNK), a family of stressactivated protein kinases, may be activated and contribute to apoptotic signal transduction when cells are exposed to multiple forms of stress such as growth factor withdrawal, excitoxic stress, ultraviolet radiation (Kurinna et al, 2004;Hamdi et al, 2005;Khelifi et al, 2005). The target proteins of JNK have the transcription factor c-Jun, which is phosphorylated and activated by JNK, forkhead transcriptional factor which is phosphorylated by JNK and then translocates to nucleus for regulating the transcription of some target genes, and some pro-apoptotic or anti-apoptotic proteins such as Bax and Bcl-2 (Kops et al, 2002;Essers et al, 2004).…”

UVB-dependent changes in the expression of fast-responding early genes is modulated by huCOP1 in keratinocytes

“…Pflegerl et al [32] reported that challenging JUNB ∆ep mice with UVB irradiation enhanced the severity of their lupus-like lesions. It has also been published that DAXX-depleted fibroblasts are resistant to UVB-and oxidative-stress-induced cell death [33]. Presumably, the absence of certain members of the huCOP1-mediated transcriptional cascade leads to an abnormal UVB response.…”