Homologue Of Tumor Suppressor P53 Research Articles

Bombyx mori homolog of tumor suppressor p53 is involved in apoptosis-mediated antiviral immunity of B. mori cells infected with nucleopolyhedrovirus

Apoptosis is important in antiviral immunity and affects viral multiplication and pathogenesis. Here, we showed that Bombyx mori cells transiently expressing B. mori homolog of the tumor suppressor p53 (Bm-p53) protein underwent apoptosis accompanied by elevated caspase-3-like protease activity and processing of B. mori Dronc (Bm-Dronc). RNAi-mediated silencing of bm-p53 expression, which significantly diminished accumulation of bm-p53 transcript and Bm-p53 protein, prevented apoptosis of B. mori cells infected with a recombinant B. mori nucleopolyhedrovirus defective in the anti-apoptotic p35 gene (vBmΔp35) and abolished the activation of caspase-3-like protease and processing of Bm-Dronc. Apoptosis in vBmΔp35-infected B. mori cells is associated with viral DNA replication, suggesting involvement of the DNA damage response. The Bm-p53 pro-apoptotic function is also found in Spodoptera frugiperda and Lymantria dispar cells. These results indicate that apoptosis induction in vBmΔp35-infected B. mori cells is a Bm-p53-mediated process promoted by the commencement of viral DNA replication.

JNK1 inhibits transcriptional and pro-apoptotic activity of TAp63γ.

TAp63γ is a homologue of tumor suppressor p53 and functions as a transcriptional factor playing key roles in cell cycle and cell apoptosis. In the present work, we find that JNK1 can physically interact with N-terminal transactivation domain (TAD) of TAp63. Overexpression of JNK1 inhibits TAp63γ-mediated transcription, while knockdown or inhibition of endogenous JNK1 increases transactivity of TAp63γ. Further study reveals that Ser12 site in TAD is critical for JNK1-mediated inhibition of TAp63γ. This JNK1-mediated inhibition can impair pro-apoptotic activity of TAp63γ. Together, we report a novel regulation of TAp63γ transactivity and pro-apoptotic activity mediated by JNK1.

JNK1 inhibits transcriptional and pro-apoptotic activity of TAp63γ

TAp63γ is a homologue of tumor suppressor p53 and functions as a transcriptional factor playing key roles in cell cycle and cell apoptosis. In the present work, we find that JNK1 can physically interact with N-terminal transactivation domain (TAD) of TAp63. Overexpression of JNK1 inhibits TAp63γ-mediated transcription, while knockdown or inhibition of endogenous JNK1 increases transactivity of TAp63γ. Further study reveals that Ser12 site in TAD is critical for JNK1-mediated inhibition of TAp63γ. This JNK1-mediated inhibition can impair pro-apoptotic activity of TAp63γ. Together, we report a novel regulation of TAp63γ transactivity and pro-apoptotic activity mediated by JNK1.

Role of p73 in Regulating Human Caspase-1 Gene Transcription Induced by Interferon-γ and Cisplatin

Caspase-1, a cysteine protease is primarily involved in proteolytic activation of proinflammatory cytokines such as interleukin-1beta. It is also involved in some forms of apoptosis. Here we have analyzed the role of p73, a homolog of tumor suppressor p53, in regulating human caspase-1 gene transcription. The caspase-1 promoter was strongly activated by p73alpha and p73beta primarily through a p53/p73 responsive site. Overexpression of p73 by transient transfection increased the caspase-1 mRNA level. Treatment of cells with cisplatin (which increases p73 protein level) resulted in increased caspase-1 promoter activity and its mRNA level. Blocking of p73 function by a dominant negative mutant reduced basal as well as cisplatin-induced caspase-1 promoter activity. Mutation of the p73 responsive site abolished cisplatin-induced activation of the promoter. Interferon-gamma induced caspase-1 promoter activity and this was reduced by p73-directed small hairpin RNA and also by a dominant negative mutant of p73. Abrogation of the p73 responsive site partially inhibited interferon-gamma-induced activation of the caspase-1 promoter. Treatment of HeLa cells with interferon-gamma resulted in an increase in p73 protein as well as its activity. Mutation of the IRF-1 binding site abolished interferon-gamma-induced caspase-1 promoter activity but p73-induced activation was only marginally reduced. IRF-1 cooperated with p73 and cisplatin cooperated with interferon-gamma in the activation of the caspase-1 promoter. Our results show that p73 is a regulator of caspase-1 gene transcription, and is required for optimal activation of the caspase-1 promoter by interferon-gamma.