Dear Editor,Ferroptosis is a non-apoptotic form of regulated cell death driven by iron-dependent phospholipid peroxidation(Chen et al.,2021).The tumor suppressor p53 promotes ferroptosis by increasing lipid peroxidati...Dear Editor,Ferroptosis is a non-apoptotic form of regulated cell death driven by iron-dependent phospholipid peroxidation(Chen et al.,2021).The tumor suppressor p53 promotes ferroptosis by increasing lipid peroxidation and reducing glutathione(GSH)levels,while it also inhibits ferroptosis by activating the expression of several ferroptosis repressors,such as FSP1 and iPLA2β,indicating the complexity of p53’s function in modulating ferroptosis in a cell-specific or context-specific manner(Liu and Gu,2022).展开更多
The tumor suppressor p53 plays an important role in the inhibition of cancer progression,particularly in response to chemotherapy or target-specific therapy.Inactivation or mutation of p53 often becomes a cancer’s ta...The tumor suppressor p53 plays an important role in the inhibition of cancer progression,particularly in response to chemotherapy or target-specific therapy.Inactivation or mutation of p53 often becomes a cancer’s tactic for drug resistance.One of the clinically applied therapeutic strategies is to inhibit poly(ADP-ribose)polymerase(PARP)activity,as PARP inhibitors are widely used for subsets of tumors with homologous recombination deficiency due to mutation of BRCA1/2 or other DNA repair-associated genes.It has been shown that p53 deficiency or mutation enhances the cytotoxicity of PARP inhibition in various tumors(Williamson et al.,2012).展开更多
The tumor-suppressive activity of p53 is largely attributed to its ability to induce cell death,including apoptosis,through transcription-dependent and transcription-independent mechanisms.On the one hand,nuclear p53 ...The tumor-suppressive activity of p53 is largely attributed to its ability to induce cell death,including apoptosis,through transcription-dependent and transcription-independent mechanisms.On the one hand,nuclear p53 transcriptionally activates the expression of a myriad of pro-apoptotic BCL-2 family genes,such as NOXA,PUMA,BID,BAD,BIK,BAX,etc.,whereas it inactivates the expression of anti-apoptotic BCL-2,BCL-XL,and MCL1,leading to mitochondrial apoptosis.On the other hand,cytoplasmic p53 also promotes mitochondrial apoptosis by directly associating with multiple BCL-2 family proteins in the mitochondria.Apoptosis-related protein in TGF-βsignaling pathway(ARTS),a mitochondria-localized pro-apoptotic protein encoded by an alternative spliced variant of the SEPT4 gene,triggers apoptosis by facilitating proteasomal degradation of BCL-2 and XIAP upon pro-apoptotic stimuli.We recently identified SEPT4/ARTS as a new p53 target gene in response to genotoxic stress.ARTS in turn binds to p53,drives its mitochondrial localization,and enhances the interaction between p53 and BCL-XL,thereby promoting mitochondrial apoptosis.This review will illustrate the mechanisms of p53-induced mitochondrial apoptosis,offer some recently discovered new insights into the functions of ARTS in regulating mitochondrial cell death,and discuss the clinical significance of ARTS in cancer and non-cancer diseases.展开更多
Although ribosomal proteins are known for playing an essential role in ribosome assembly and protein translation,their ribosomeindependent functions have also been greatly appreciated.Over the past decade,more than a ...Although ribosomal proteins are known for playing an essential role in ribosome assembly and protein translation,their ribosomeindependent functions have also been greatly appreciated.Over the past decade,more than a dozen of ribosomal proteins have been found to activate the tumor suppressor p53 pathway in response to ribosomal stress.In addition,these ribosomal proteins are involved in various physiological and pathological processes.This review is composed to overview the current understanding of how ribosomal stress provokes the accumulation of ribosome-free ribosomal proteins,as well as the ribosome-independent functions of ribosomal proteins in tumorigenesis,immune signaling,and development.Wealso propose the potential of applying these pieces of knowledge to the development of ribosomal stress-based cancer therapeutics.展开更多
基金supported by the National Natural Science Foundation of China(82072879,82273098,81874053,82173022)General Program of Open Science Foundation of Jiangxi Cancer Hospital(2021J04)HL was in part funded by the Reynolds and Ryan Families Chair fund in Transitional Cancer at Tulane.
文摘Dear Editor,Ferroptosis is a non-apoptotic form of regulated cell death driven by iron-dependent phospholipid peroxidation(Chen et al.,2021).The tumor suppressor p53 promotes ferroptosis by increasing lipid peroxidation and reducing glutathione(GSH)levels,while it also inhibits ferroptosis by activating the expression of several ferroptosis repressors,such as FSP1 and iPLA2β,indicating the complexity of p53’s function in modulating ferroptosis in a cell-specific or context-specific manner(Liu and Gu,2022).
文摘The tumor suppressor p53 plays an important role in the inhibition of cancer progression,particularly in response to chemotherapy or target-specific therapy.Inactivation or mutation of p53 often becomes a cancer’s tactic for drug resistance.One of the clinically applied therapeutic strategies is to inhibit poly(ADP-ribose)polymerase(PARP)activity,as PARP inhibitors are widely used for subsets of tumors with homologous recombination deficiency due to mutation of BRCA1/2 or other DNA repair-associated genes.It has been shown that p53 deficiency or mutation enhances the cytotoxicity of PARP inhibition in various tumors(Williamson et al.,2012).
基金supported by the National Natural Science Foundation of China(82072879 and 82273098 to X.Z.,82173022 to Q.H.,and 82060278 to J.C.)the Reynolds and Ryan Families Chair Fund in Transitional Cancer at Tulane to H.L.
文摘The tumor-suppressive activity of p53 is largely attributed to its ability to induce cell death,including apoptosis,through transcription-dependent and transcription-independent mechanisms.On the one hand,nuclear p53 transcriptionally activates the expression of a myriad of pro-apoptotic BCL-2 family genes,such as NOXA,PUMA,BID,BAD,BIK,BAX,etc.,whereas it inactivates the expression of anti-apoptotic BCL-2,BCL-XL,and MCL1,leading to mitochondrial apoptosis.On the other hand,cytoplasmic p53 also promotes mitochondrial apoptosis by directly associating with multiple BCL-2 family proteins in the mitochondria.Apoptosis-related protein in TGF-βsignaling pathway(ARTS),a mitochondria-localized pro-apoptotic protein encoded by an alternative spliced variant of the SEPT4 gene,triggers apoptosis by facilitating proteasomal degradation of BCL-2 and XIAP upon pro-apoptotic stimuli.We recently identified SEPT4/ARTS as a new p53 target gene in response to genotoxic stress.ARTS in turn binds to p53,drives its mitochondrial localization,and enhances the interaction between p53 and BCL-XL,thereby promoting mitochondrial apoptosis.This review will illustrate the mechanisms of p53-induced mitochondrial apoptosis,offer some recently discovered new insights into the functions of ARTS in regulating mitochondrial cell death,and discuss the clinical significance of ARTS in cancer and non-cancer diseases.
基金H.L.was supported by NIH-NCI grants CA095441 and CA172468the Reynolds and Ryan Families chair fund.
文摘Although ribosomal proteins are known for playing an essential role in ribosome assembly and protein translation,their ribosomeindependent functions have also been greatly appreciated.Over the past decade,more than a dozen of ribosomal proteins have been found to activate the tumor suppressor p53 pathway in response to ribosomal stress.In addition,these ribosomal proteins are involved in various physiological and pathological processes.This review is composed to overview the current understanding of how ribosomal stress provokes the accumulation of ribosome-free ribosomal proteins,as well as the ribosome-independent functions of ribosomal proteins in tumorigenesis,immune signaling,and development.Wealso propose the potential of applying these pieces of knowledge to the development of ribosomal stress-based cancer therapeutics.
