Regulation Mechanism Of PML And PML-NBs In Cell Apoptosis

Numerous cellular mechanism enforce the rule "better dead than wrong", which means that cells that have a damaged genome or are afflicted by many disorders will be aborted by apoptosis-thereby maintaining normal economy functions. Once there are obstacles in apoptotic regulation or disorders in cell homestasis, diseases such as tumor, autoimmune diseases, neurodegenerative diseases will emerge. Therefore, cell apoptosis is a study hotspot in life science area. Recent researches showed that PML (promyelocytic leukemia) exerts key function in apoptotic signal transduction. Loss of PML can strongly suppress apoptosis induced by ionizing radiation, CD95/Fas, ceramide, TNF, IFN. Those results revealed that PML can form PML-NBs, an associated with matrix, dynamic, sub-nuclear multi-protein structure, which is necessary for PML exerting function by monomerizing and recruiting other proteins. As a function unit of interchromatin compartment, PML-NBs can satisfy the time-space demand on high level of the regulation of gene expression. Bernardi summarize the functions of PML and PML-NBs in apoptosis regulation precisely: PML and PML-NBs act as molecular hubs for the induction and/or reinforcement of programmed cell death through a selective and dynamic regulation of proapoptotic transcriptional events.Transcriptional regulation molecules, p53 and Daxx that have important roles in cell apoptosis regulation can localize into PML-NBs. Interactions among three molecules form PML-p53-Daxx transcriptional regulatory network that exerts important functions in apoptotic regulation. Researches about this transcriptional regulatory network revealed: Specific sites of p53 are phosphorylated or acethylated after recruited into PML-NBs in DNA damage response. These modifications can facilitate p53 transcriptional activity and ability to induce cell apoptosis. To Daxx, localizing to PML-NBs is necessary for its apoptosis inducing function. At the same time, Daxx can regulate p53 transcriptional activity. This regulation also can be regulated by PML. So...