JPOST Repositoryapplication/xmlhttps://storage.jpostdb.org/JPST001399/files/160707_hata_160707_Li_N_02_refseq_human8_P_CarbamidoM_PRS.xlsxhttps://storage.jpostdb.org/JPST001399/files/151222_hata_151222_arai_P_02_refseq_human8_P_CarbamidoM_PRS.xlsxhttps://storage.jpostdb.org/JPST001399/files/150902_hata_150902_arai_P_02_refseq_human8_P_CarbamidoM_PRS.xlsxhttps://storage.jpostdb.org/JPST001399/files/150219_hata_150219_arai_P_02_refseq_human8_P_CarbamidoM_PRS.xlsxhttps://storage.jpostdb.org/JPST001399/files/161124_hata_161124_fujikawa_03_refseq_human8_CarbamidoM_PRS.xlsxhttps://storage.jpostdb.org/JPST001399/files/151124_hata_151120_Li_P_02_refseq_human8_P_CarbamidoM_PRS.xlsxhttps://storage.jpostdb.org/JPST001399/files/170406_hata_170406_fujikawa_02_refseq_human8_CarbamidoM_PRS.xlsxhttps://storage.jpostdb.org/JPST001399/files/160630_hata_160630_Li_P_02_refseq_human8_P_CarbamidoM_PRS.xlsxhttps://storage.jpostdb.org/JPST001399/files/160322_hata_160322_Li_02_refseq_human8_P_CarbamidoM_PRS.xlsxhttps://storage.jpostdb.org/JPST001399/files/170113_hata_170113_fujikawa_03_refseq_human8_CarbamidoM_PRS.xlsxhttps://storage.jpostdb.org/JPST001399/files/160322_Li_02.rawhttps://storage.jpostdb.org/JPST001399/files/160707_Li_N_02.rawhttps://storage.jpostdb.org/JPST001399/files/160630_Li_P_02.rawhttps://storage.jpostdb.org/JPST001399/files/150219_arai_P_02.rawhttps://storage.jpostdb.org/JPST001399/files/151222_arai_P_02.rawhttps://storage.jpostdb.org/JPST001399/files/161124_fujikawa_03.rawhttps://storage.jpostdb.org/JPST001399/files/170113_fujikawa_03.rawhttps://storage.jpostdb.org/JPST001399/files/150902_arai_P_02.rawhttps://storage.jpostdb.org/JPST001399/files/170406_fujikawa_02.rawhttps://storage.jpostdb.org/JPST001399/files/151120_Li_P_02.rawprimaryOK200ProteomicsMasaaki OyamaHomo Sapiens (human)https://repository.jpostdb.org/entry/JPST001399The Institute of Medical Science, The University of TokyojPOSTCytoplasmic stress granules (SGs) are phase-separated membrane-less organelles that form in response to various stress stimuli. SGs are mainly composed of non-canonical stalled 48S preinitiation complexes. In addition, many other proteins also accumulate into SGs, but the list is still incomplete. SG assembly suppresses apoptosis and promotes cell survival under stress. Furthermore, hyperformation of SGs is frequently observed in various human cancers and accelerates tumor development and progression by reducing stress-induced damage of cancer cells. Therefore, they are of clinical importance. However, the precise mechanism underlying SG-mediated inhibition of apoptosis remains ill-defined. Here, using a proximity-labeling proteomic approach, we comprehensively analyzed SG-resident proteins and identified the executioner caspases, caspase-3 and -7, as SG components. We demonstrate that accumulation of caspase-3/7 into SGs is mediated by evolutionarily conserved amino acid residues within their large catalytic domains and inhibits caspase activities and consequent apoptosis induced by various stresses. Expression of an SG-localization-deficient caspase-3 mutant in cells largely counteracted the anti-apoptotic effect of SGs, whereas enforced relocalization of the caspase-3 mutant to SGs restored it. Thus, SG-mediated sequestration of executioner caspases is a mechanism underlying the broad cytoprotective function of SGs. Furthermore, using a mouse xenograft tumor model, we show that this mechanism prevents cancer cells from apoptosis in tumor tissues, thereby promoting cancer progression. Our results reveal the functional crosstalk between SG-mediated cell survival and caspase-mediated cell death signaling pathways and delineate a molecular mechanism that dictates cell-fate decisions under stress and promotes tumorigenesis.Stress granule formation inhibits stress-induced apoptosis by selectively sequestering executioner caspases.Fujikawa Daichi D, Nakamura Takanori T, Yoshioka Daisuke D, Li Zizheng Z, Moriizumi Hisashi H, Taguchi Mari M, Tokai-Nishizumi Noriko N, Kozuka-Hata Hiroko H, Oyama Masaaki M, Takekawa Mutsuhiro Msingle-organism biosynthetic process, Stress Granule, stress granule, Caspase-Dependent Apoptosis, apoptosis, storage, caspase-dependent programmed cell death, P-body, Caspase Dependent Apoptosis, apoptosis activator activity, Granule, retention, Classic Apoptoses, Intrinsic Pathway Apoptoses, Intrinsic Pathway Apoptosis, signaling (initiator) caspase activity, cytoplasmic mRNP granule, induction of apoptosis, induction of apoptosis by p53, Extrinsic Pathway Apoptoses, Intrinsic Pathway, Classic, Classic Apoptosis, Extrinsic Pathway Apoptosis, Programmed Cell Death, Stress, Classical Apoptosis, Extrinsic Pathway, commitment to apoptosis, sequestering, Caspase., Caspase-Dependent, Type I, Classical, Apoptoses, multicellular organismal biosynthetic process, ApoptosisMass Spectrum Analysis, Spectroscopy, Mass Spectrum, MS, Analyses, Stress, Mass, Spectrometry, Analysis, Spectrum Analyses, Stress Granule., Granule, Mass Spectrum Analyses, Spectrum Analysis, Mass SpectroscopyMass Spectrum Analysis, Spectroscopy, Mass Spectrum, MS, Analyses, Mass, Mass., Spectrometry, Analysis, Spectrum Analyses, Mass Spectrum Analyses, Spectrum Analysis, Mass SpectroscopyForms, type 1, CPP-32, single-organism developmental process, Laboratory, acetylglucosaminyltransferase-like protein, Heterograft, postnatal development, Aminosaeure, Mus domesticus, Mbp1, growth and development, Organelle, TRANSPL HETEROL, Viabilities, Tumor, composed of, House Mouse, MAGE-E1 antigen, dmTAF[[II]]230, Membrane Tissues, Extrinsic Pathway Apoptoses, CASP-3, establishment and maintenance of substrate location, myd, WMS, Viability, Divorced, mldy, amino acids, Man (Taxonomy), like-acetylglucosaminyltransferase, TFIID TAF250, cel, FATE, membrane region, Tissue, Mbp-1, composition, Swiss Mice, Divorces, pro-survival, Marfanoid craniosynostosis syndrome, Intrinsic Pathway Apoptosis, Xenotransplantations, Schinzel-Giedion midface retraction syndrome, Schinzel Giedion midface-retraction syndrome, HCA1, malignant neoplasm, Classic, Classical Apoptosis, apoptosis inhibitor activity, xenotransplant, Malignancies, necrosis, house mouse, GPHYSD2, SGS, Sgs, single organism signaling, Tumors, Membrane Tissue, establishment and maintenance of substance location, dTAF[[II]]230, craniosynostosis with arachnodactyly and abdominal hernias, wide/broad, Caspase-Dependent Apoptosis, gyltl1b-b, Caspase-3, Aminokarbonsaeure, Modern, mouse, incomplete, TAF200, integral to membrane, Yama, TAFII-250, TAF250/230, Lice, results, ACMICD, abolished, single organism localization, TAFII250, signaling (initiator) caspase activity, Benign, induction of apoptosis, CT43., Intrinsic Pathway, MDDGA6, Extrinsic Pathway Apoptosis, mKIAA0609, DAMAGE, Hepatocellular carcinoma-associated protein 1, Caspase-Dependent, KIAA0609, Heterologous Transplantations, acetylglucosaminyltransferase-like 1A, fg, Amino Acid, Acid, Mus musculus, Xenograft, Xenotransplantation, gyltl1b, Transplantation, mice, content, Shprintzen-Goldberg craniosynostosis syndrome, mdc1d, Swiss Mouse, Benign Neoplasms, MASS, negative regulation of apoptosis, Xenografts, CG17603, Granule, LARGE_HUMAN, TAF[[II]], human, Malignant Neoplasms, domesticus, Schinzel Giedion syndrome, Intrinsic Pathway Apoptoses, SG assembly, MDC1D, wide, inhibition of apoptosis, induction of apoptosis by p53, enr, Taf250, Marfanoid disorder with craniosynostosis type 1, SR3-5, Extrinsic Pathway, Acids, Mouse, CPP32, other neoplasm, Classical, mMage-e1, Apoptoses, TAF230, establishment and maintenance of cellular component location, SKV, Procaspase-3, d230, human being, Neoplasms, caspase-dependent programmed cell death, Benign Neoplasm, Aminocarbonsaeure, FBN, Gene, Caspase Dependent Apoptosis, dTAFII250, broad, Transplantations, Malignant, EfW1, LARGE1, froggy, Gyltl1a, heterologous transplantation, Human, Homo sapiens, House, dmTAF1, ECTOL1, Taf230, integral component of membrane, Survival, Gene Products, establishment and maintenance of position, Mus musculus domesticus, Marfanoid disorder with craniosynostosis, Apopain, Type I, Separated, Mice, Man, TAF250, Taf200, dTAF[[II]]250, Malignancy, Tissues, Swiss, cell, MDDGB6, Heterografts, A830040C14Rik, Taf1p, labeling, AC-3, LARGE, AI847422, apoptosis activator activity, OCTD, Neoplasias, BPFD#36, dTAF250, Caspase, Procaspase 3, Classic Apoptosis, accidental cell death, region of membrane, TAF, Heterologous, Apoptosis, Cancer, membrane, TAF[[II]]250, Stress Granule, Malignant Neoplasm, Proteins, Alpha-dystrobrevin-associated MAGE Protein, l(3)84Ab, CASP3, function, BG:DS00004.13, Marfanoid-craniosynostosis syndrome, compositionality, Cell, dTAF230, Cell Viabilities, development, MT, XENOTRANSPL, Mus, p230, Programmed Cell Death, Protein, whole membrane, Neoplasm, TAF[[II]]250/230, TFIID, MFS1, establishment and maintenance of localization, Death, WMS2, Pro Caspase 3, Taf[[II]]250, Separation, transmembrane, primary cancer, TAF[[II]]230, apoptosis, RGD1560259, Separations, postnatal growth, CC3, House Mice, HETEROL TRANSPL, TAF[II]250, Cancers, single-organism localization, Membrane, Amino, malignant tumor, Shprintzen-Goldberg marfanoid syndrome, Laboratory Mice, Protein Gene Products, Classic Apoptoses, Gene Proteins, SCA-1, DmelCG17603, localisation, like-glycosyltransferase, signalling process, Modern Man, Pro-Caspase-3, Stress, SSKS, structure, commitment to apoptosis, Cell Viability, growth, Laboratory Mouse, Neoplasia, glycosyltransferase-like protein LARGE1, TAF1falseBioID-based mass spectrometry dataBioID-based mass spectrometry data on stress granulesThu Apr 20 00:00:00 GMT+01:00 2023PXD030039960637119817