title: p53 facilitates BH3-only BID nuclear export to induce apoptosis in the irrepairable DNA damage response.
abstract: Over the past decade, the BH3-only BID likes p53, has emerged as a central player in linking death signals through surface death receptors to the core apoptotic mitochondrial pathway and life signals through cell cycle arrest. Recent studies indicate that pro-apoptotic activation of BID may be negatively regulated by its phosphorylation in response to DNA damage. BID itself plays a role in cell cycle checkpoint response, in DNA repair, or in integrating apoptosis and the DNA damage response, which indicate BID is a nuclear-cytoplasmic protein. However, BID does not have any obvious nuclear localization signals (NLS), and only carries nuclear export signals (NES). Mutating BID NES does not affect the nuclear exit of BID, suggesting that BID NES does not seem to function as a NES. Therefore, BID is transported into the nucleus and its export is probably mediated by other NES-carrying proteins. As a well-characterized transcription factor, p53 carries typical NLS and NES. Bid is transcriptionally regulated by p53, and both can be exported from nucleus to the mitochondria in response to DNA damage. Moreover, p53 can, through the interaction with BID in the mitochondria to induce apoptosis. Given the above background, we hypothesize that p53 facilitates BID nuclear export to induce apoptosis in response to irreparable DNA damage.
authors.affiliation: Cancer Research Center, Medical College of Xiamen University, Xiamen 361005, PR China. gangsongsd@xmu.edu.cn
authors.forename: Gang
authors.initials: G
authors.lastname: Song
authors.forename: Weiwei
authors.initials: W
authors.lastname: Wang
authors.forename: Tianhui
authors.initials: T
authors.lastname: Hu
mesh_terms: D017209:Apoptosis / Q000502:physiology*; D051023:BH3 Interacting Domain Death Agonist Protein / Q000235:genetics / Q000378:metabolism*; D004249:DNA Damage; D049790:Nuclear Export Signals; D021381:Protein Transport; D016159:Tumor Suppressor Protein p53 / Q000502:physiology*
chemical_list: D051023:BH3 Interacting Domain Death Agonist Protein; D049790:Nuclear Export Signals; D016159:Tumor Suppressor Protein p53