Thandapani, P. et al. Valine tRNA levels and availability regulate complex I assembly in leukaemia. Nature 601, 428â433 (2022).
Taya, Y. et al. Depleting dietary valine permits nonmyeloablative mouse hematopoietic stem cell transplantation. Science 354, 1152â1155 (2016).
Tarlungeanu, D. C. et al. Impaired amino acid transport at the blood brain barrier is a cause of autism spectrum disorder. Cell 167, 1481â1494.e18 (2016).
Chantranupong, L., Wolfson, R. L. & Sabatini, D. M. Nutrient-sensing mechanisms across evolution. Cell 161, 67â83 (2015).
Hu, X. & Guo, F. Amino acid sensing in metabolic homeostasis and health. Endocr. Rev. 42, 56â76 (2021).
He, X. D. et al. Sensing and transmitting intracellular amino acid signals through reversible lysine aminoacylations. Cell Metab. 27, 151â166.e6 (2018).
Wang, S. et al. Lysosomal amino acid transporter SLC38A9 signals arginine sufficiency to mTORC1. Science 347, 188â194 (2015).
Wolfson, R. L. et al. Sestrin2 is a leucine sensor for the mTORC1 pathway. Science 351, 43â48 (2016).
Wolfson, R. L. & Sabatini, D. M. The dawn of the age of amino acid sensors for the mTORC1 pathway. Cell Metab. 26, 301â309 (2017).
Chen, J. et al. SAR1B senses leucine levels to regulate mTORC1 signalling. Nature 596, 281â284 (2021).
Liu, G. Y., Jouandin, P., Bahng, R. E., Perrimon, N. & Sabatini, D. M. An evolutionary mechanism to assimilate new nutrient sensors into the mTORC1 pathway. Nat Commun. 15, 2517 (2024).
Gu, X. et al. SAMTOR is an S-adenosylmethionine sensor for the mTORC1 pathway. Science 358, 813â818 (2017).
Jiang, C. et al. PRMT1 orchestrates with SAMTOR to govern mTORC1 methionine sensing via Arg-methylation of NPRL2. Cell Metab. 35, 2183â2199.e7 (2023).
Sivanand, S. & Vander Heiden, M. G. Emerging roles for branched-chain amino acid metabolism in cancer. Cancer Cell 37, 147â156 (2020).
Wang, Z. et al. Methionine is a metabolic dependency of tumor-initiating. cells. Nat. Med. 25, 825â837 (2019).
Pandey, U. B. et al. HDAC6 rescues neurodegeneration and provides an essential link between autophagy and the UPS. Nature 447, 859â863 (2007).
Kawaguchi, Y. et al. The deacetylase HDAC6 regulates aggresome formation and cell viability in response to misfolded protein stress. Cell 115, 727â738 (2003).
Hubbert, C. et al. HDAC6 is a microtubule-associated deacetylase. Nature 417, 455â458 (2002).
Zhang, T. et al. HDAC6 regulates primordial follicle activation through mTOR signaling pathway. Cell Death Dis. 12, 559 (2021).
Liu, Y., Peng, L., Seto, E., Huang, S. & Qiu, Y. Modulation of histone deacetylase 6 (HDAC6) nuclear import and tubulin deacetylase activity through acetylation. J. Biol. Chem. 287, 29168â29174 (2012).
Wang, Z. et al. Genome-wide mapping of HATs and HDACs reveals distinct functions in active and inactive genes. Cell 138, 1019â1031 (2009).
Bertos, N. R. et al. Role of the tetradecapeptide repeat domain of human histone deacetylase 6 in cytoplasmic retention. J. Biol. Chem. 279, 48246â48254 (2004).
Jones, P. A. Functions of DNA methylation: islands, start sites, gene bodies and beyond. Nat. Rev. Genet. 13, 484â492 (2012).
Tahiliani, M. et al. Conversion of 5-methylcytosine to 5-hydroxymethylcytosine in mammalian DNA by MLL partner TET1. Science 324, 930â935 (2009).
Zhang, H. et al. TET1 is a DNA-binding protein that modulates DNA methylation and gene transcription via hydroxylation of 5-methylcytosine. Cell Res. 20, 1390â1393 (2010).
He, Y. F. et al. Tet-mediated formation of 5-carboxylcytosine and its excision by TDG in mammalian DNA. Science 333, 1303â1307 (2011).
Schutsky, E. K. et al. Nondestructive, base-resolution sequencing of 5-hydroxymethylcytosine using a DNA deaminase. Nat. Biotechnol. https://doi.org/10.1038/nbt.4204 (2018).
Sun, J. et al. SIRT1 activation disrupts maintenance of myelodysplastic syndrome stem and progenitor cells by restoring TET2 function. Cell Stem Cell 23, 355â369.e9 (2018).
Wang, D. et al. Active DNA demethylation promotes cell fate specification and the DNA damage response. Science 378, 983â989 (2022).
Shukla, V. et al. TET deficiency perturbs mature B cell homeostasis and promotes oncogenesis associated with accumulation of G-quadruplex and R-loop structures. Nat. Immunol. 23, 99â108 (2022).
An, J. et al. Acute loss of TET function results in aggressive myeloid cancer in mice. Nat. Commun. 6, 10071 (2015).
Kafer, G. R. et al. 5-Hydroxymethylcytosine marks sites of DNA damage and promotes genome stability. Cell Rep. 14, 1283â1292 (2016).
Oswald, J. et al. Active demethylation of the paternal genome in the mouse zygote. Curr. Biol. 10, 475â478 (2000).
Fry, D. W. et al. Specific inhibition of cyclin-dependent kinase 4/6 by PD 0332991 and associated antitumor activity in human tumor xenografts. Mol. Cancer Ther. 3, 1427â1438 (2004).
Groelly, F. J., Fawkes, M., Dagg, R. A., Blackford, A. N. & Tarsounas, M. Targeting DNA damage response pathways in cancer. Nat. Rev. Cancer 23, 78â94 (2023).
Thomas, A. et al. Therapeutic targeting of ATR yields durable regressions in small cell lung cancers with high replication stress. Cancer Cell 39, 566â579.e7 (2021).
Harding, S. M. et al. Mitotic progression following DNA damage enables pattern recognition within micronuclei. Nature 548, 466â470 (2017).
Nishihira, T. et al. Anti-cancer therapy with valine-depleted amino acid imbalance solution. Tohoku J. Exp. Med. 156, 259â270 (1988).
Farmer, H. et al. Targeting the DNA repair defect in BRCA mutant cells as a therapeutic strategy. Nature 434, 917â921 (2005).
She, P. et al. Disruption of BCATm in mice leads to increased energy expenditure associated with the activation of a futile protein turnover cycle. Cell Metab. 6, 181â194 (2007).
Ananieva, E. A. & Wilkinson, A. C. Branched-chain amino acid metabolism in cancer. Curr. Opin. Clin. Nutr. Metab. Care 21, 64â70 (2018).
Jegga, A. G., Inga, A., Menendez, D., Aronow, B. J. & Resnick, M. A. Functional evolution of the p53 regulatory network through its target response elements. Proc. Natl Acad. Sci. USA 105, 944â949 (2008).
Knaus, L. S. et al. Large neutral amino acid levels tune perinatal neuronal excitability and survival. Cell 186, 1950â1967.e25 (2023).
Kanarek, N., Petrova, B. & Sabatini, D. M. Dietary modifications for enhanced cancer therapy. Nature 579, 507â517 (2020).
Gao, X. et al. Dietary methionine influences therapy in mouse cancer models and alters human metabolism. Nature 572, 397â401 (2019).
Li, T. et al. Histone deacetylase 6 in cancer. J. Hematol. Oncol. 11, 111 (2018).
Wang, X. et al. AMPK promotes SPOP-mediated NANOG degradation to regulate prostate cancer cell stemness. Dev. Cell 48, 345â360.e7 (2019).
Kulak, N. A., Pichler, G., Paron, I., Nagaraj, N. & Mann, M. Minimal, encapsulated proteomic-sample processing applied to copy-number estimation in eukaryotic cells. Nat. Methods 11, 319â324 (2014).
Wisniewski, J. R., Zougman, A., Nagaraj, N. & Mann, M. Universal sample preparation method for proteome analysis. Nat. Methods 6, 359â362 (2009).
Demichev, V., Messner, C. B., Vernardis, S. I., Lilley, K. S. & Ralser, M. DIA-NN: neural networks and interference correction enable deep proteome coverage in high throughput. Nat. Methods 17, 41â44 (2020).
Nakagawa, T. et al. CRL4VprBP E3 ligase promotes monoubiquitylation and chromatin binding of TET dioxygenases. Mol. Cell 57, 247â260 (2015).
Yang, J. et al. Highly sensitive and selective determination of bisphenol-A using peptide-modified gold electrode. Biosens. Bioelectron. 61, 38â44 (2014).
Su, W. Q., Cho, M., Nam, J. D., Choe, W. S. & Lee, Y. Highly sensitive electrochemical lead ion sensor harnessing peptide probe molecules on porous gold electrodes. Biosens. Bioelectron. 48, 263â269 (2013).
Qin, J., Kim, S., Cho, M. & Lee, Y. Hierarchical and ultra-sensitive amyloid beta oligomer sensor for practical applications. Chem. Eng. J. 401, 126055 (2020).
Qin, J., Jo, D. G., Cho, M. & Lee, Y. Monitoring of early diagnosis of Alzheimerâs disease using the cellular prion protein and poly(pyrrole-2-carboxylic acid) modified electrode. Biosens. Bioelectron. 113, 82â87 (2018).
Fang, S. et al. Tet inactivation disrupts YY1 binding and long-range chromatin interactions during embryonic heart development. Nat. Commun. 10, 4297 (2019).
Wu, H., Wu, X., Shen, L. & Zhang, Y. Single-base resolution analysis of active DNA demethylation using methylase-assisted bisulfite sequencing. Nat. Biotechnol. 32, 1231â1240 (2014).
Wu, H., Wu, X. & Zhang, Y. Base-resolution profiling of active DNA demethylation using MAB-seq and caMAB-seq. Nat. Protoc. 11, 1081â1100 (2016).
Qu, J., Zhou, M., Song, Q., Hong, E. E. & Smith, A. D. MLML: consistent simultaneous estimates of DNA methylation and hydroxymethylation. Bioinformatics 29, 2645â2646 (2013).
Canela, A. et al. DNA breaks and end resection measured genome-wide by end sequencing. Mol. Cell 63, 898â911 (2016).
