Siva-1, as a p53-inducible gene, has been shown to induce extensive apoptosis in a number of different cell lines. Recent evidence suggests that Siva-1 functions as a part of the auto-regulatory feedback loop that restrains p53 through facilitating Mdm2-mediated p53 degradation. Also, Siva-1 plays an important role in suppressing tumor metastasis. Here we review the current understanding of Siva-1-mediated apoptotic signaling pathway. We also add comments on the p53-Siva-1 feedback loop, the novel function of Siva-1 in suppressing tumor metastasis, and their potential implications.
Apoptosis ; Apoptosis Regulatory Proteins ; metabolism ; Feedback, Physiological ; Humans ; Models, Biological ; Neoplasm Metastasis ; Neoplasms ; pathology ; Proto-Oncogene Proteins c-mdm2 ; metabolism ; Signal Transduction ; Tumor Suppressor Protein p53 ; metabolism

Apoptotic regulation is critical to organismal homeostasis and protection against many human disease processes such as cancer. Significant research efforts over the past several decades have illuminated many signaling molecules and effecter proteins responsible for this form of programmed cell death. Recent evidence suggests that transfer RNA (tRNA) regulates apoptotic sensitivity at the level of cytochrome c-mediated apoptosome formation. This finding unexpectedly places tRNA at the nexus of cellular biosynthesis and survival. Here we review the current understanding of both the apoptotic machinery and tRNA biology. We describe the evidence linking tRNA and cytochrome c in depth, and speculate on the implications of this link in cell biology.
Animals ; Apoptosis ; genetics ; physiology ; Caspase 9 ; physiology ; Cytochromes c ; physiology ; Humans ; Models, Biological ; Nucleic Acid Conformation ; RNA, Transfer ; chemistry ; genetics ; physiology