A Preliminary Investigation On Actin's Role In Functional Regulation Of P53.

Actin and actin-binding factors have been implicated in nuclear processes, such as chromatin remodelling, mRNA processing and export, and transcription. Various lines of evidence suggest that nuclear actin is required for efficient transcription by RNA polymerases I, II and III. Nuclear actin seems to function in several steps of the transcription process, particularly during initiation complex assembly and transcription elongation. However, the mechanisms involved are not understood, and so far, there is no evidence that the interaction between transcriptional regulators and actin may function in transcription.The tumor suppressor protein P53 is a highly efficient transcription factor that can activate the transcription of a wide range of P53 downstream genes involved in various activities, including cell-cycle control, DNA repair, genome stability, apoptosis, cell differentiation, cell senescence and angiogenesis inhibition. Having a short half-life, P53 appears to be present at low levels and exists in a latent, inactive form in unstressed cells. When the cell is confronted with stress, however, different pathways lead to post-translational modification and stabilization of P53. P53 accumulates in the nucleus where it forms a homotetrameric complex. Only tetrameric P53 seems to be fully active as a transcriptional activator or repressor of distinct target genes.In this article, we mainly discussed whether actin functions in P53 induced physiological pathways following DNA damage. Immunofluorescence experiments indicated that it is G-actin not F-actin that shows spatial and temporal synchronization with P53 after UV radiation. Stimulation experiments using actin depolymerization inhibition drug jasplakinolide and actin polymerization inhibition drugs swinholideA , cytochalasinD and latrunculinB implied that actin is involved in the regulation of P53 import. Dual luciferase assays in saos2 cells showed that cotransfection of actin and P53 plasmids leads to the promotion of P53-mediated p21 gene transcription, transfection of P53 plasmids following jasplakinolide treatment gets the opposite results. Dual luciferase assays in NIH3T3 cells demonstrated that transfection of actin plasmids as well as the treatment with doxorubicin can promote the transcription of p21 gene. In a conclusion, the nuclear G-actin can work in coordination with P53 in the regulation of gene transcription.