Interplay between acetylation and ubiquitination controls PSAT1 protein stability in lung adenocarcinoma.


Journal

Communications biology
ISSN: 2399-3642
Titre abrégé: Commun Biol
Pays: England
ID NLM: 101719179

Informations de publication

Date de publication:
21 Oct 2024
Historique:
received: 15 05 2024
accepted: 11 10 2024
medline: 22 10 2024
pubmed: 22 10 2024
entrez: 21 10 2024
Statut: epublish

Résumé

Serine is essential to maintain maximal growth and proliferation of cancer cells by providing adequate intermediate metabolites and energy. Phosphoserine aminotransferase 1 (PSAT1) is a key enzyme in de novo serine synthesis. However, little is known about the mechanisms underlying PSAT1 degradation. We found that acetylation was the switch that regulated the degradation of PSAT1 in lung adenocarcinoma (LUAD). Deacetylation of PSAT1 on Lys51 by histone deacetylase 7 (HDAC7) enhanced the interaction between PSAT1 and the deubiquitinase ubiquitin-specific processing protease 14 (USP14), leading to the deubiquitination and stabilization of PSAT1; while acetylation of PSAT1 promoted its interaction with the E3 ligase ubiquitination factor E4B (UBE4B), leading to proteasomal degradation. Acetylation of PSAT1 on Lys51 regulated serine metabolism and tumor proliferation in LUAD. Thus, acetylation and ubiquitination cooperatively regulated the protein homeostasis of PSAT1. In conclusion, our study reveals a key regulatory mechanism for maintaining PSAT1 protein homeostasis in LUAD.

Identifiants

pubmed: 39433916
doi: 10.1038/s42003-024-07051-2
pii: 10.1038/s42003-024-07051-2
doi:

Substances chimiques

phosphoserine aminotransferase EC 2.6.1.52
Transaminases EC 2.6.1.-

Types de publication

Journal Article

Langues

eng

Sous-ensembles de citation

IM

Pagination

1365

Subventions

Organisme : National Natural Science Foundation of China (National Science Foundation of China)
ID : 82273258

Informations de copyright

© 2024. The Author(s).

Références

Sun, L., Suo, C., Li, S. T., Zhang, H. & Gao, P. Metabolic reprogramming for cancer cells and their microenvironment: beyond the Warburg effect. Biochim. Biophys. Acta Rev. Cancer 1870, 51–66 (2018).
pubmed: 29959989 doi: 10.1016/j.bbcan.2018.06.005
DeBerardinis, R. J. Serine metabolism: some tumors take the road less traveled. Cell Metab. 14, 285–286 (2011).
pubmed: 21907134 pmcid: 3172581 doi: 10.1016/j.cmet.2011.08.004
Newman, A. C. & Maddocks, O. D. K. Serine and functional metabolites in cancer. Trends Cell Biol. 27, 645–657 (2017).
pubmed: 28601431 doi: 10.1016/j.tcb.2017.05.001
Yang, M. & Vousden, K. H. Serine and one-carbon metabolism in cancer. Nat. Rev. Cancer 16, 650–662 (2016).
pubmed: 27634448 doi: 10.1038/nrc.2016.81
Amelio, I., Cutruzzola, F., Antonov, A., Agostini, M. & Melino, G. Serine and glycine metabolism in cancer. Trends Biochem. Sci. 39, 191–198 (2014).
pubmed: 24657017 pmcid: 3989988 doi: 10.1016/j.tibs.2014.02.004
Zhang, W. C. et al. Glycine decarboxylase activity drives non-small cell lung cancer tumor-initiating cells and tumorigenesis. Cell 148, 259–272 (2012).
pubmed: 22225612 doi: 10.1016/j.cell.2011.11.050
Possemato, R. et al. Functional genomics reveal that the serine synthesis pathway is essential in breast cancer. Nature 476, 346–350 (2011).
pubmed: 21760589 pmcid: 3353325 doi: 10.1038/nature10350
Ye, J. et al. Pyruvate kinase M2 promotes de novo serine synthesis to sustain mTORC1 activity and cell proliferation. Proc. Natl Acad. Sci. USA 109, 6904–6909 (2012).
pubmed: 22509023 pmcid: 3345000 doi: 10.1073/pnas.1204176109
DeNicola, G. M. et al. NRF2 regulates serine biosynthesis in non-small cell lung cancer. Nat. Genet. 47, 1475–1481 (2015).
pubmed: 26482881 pmcid: 4721512 doi: 10.1038/ng.3421
Sun, L. et al. cMyc-mediated activation of serine biosynthesis pathway is critical for cancer progression under nutrient deprivation conditions. Cell Res. 25, 429–444 (2015).
pubmed: 25793315 pmcid: 4387561 doi: 10.1038/cr.2015.33
Ding, J. et al. The histone H3 methyltransferase G9A epigenetically activates the serine-glycine synthesis pathway to sustain cancer cell survival and proliferation. Cell Metab. 18, 896–907 (2013).
pubmed: 24315373 doi: 10.1016/j.cmet.2013.11.004
Wang, H. et al. Overexpression of PSAT1 regulated by G9A sustains cell proliferation in colorectal cancer. Signal Transduct. Target. Ther. 5, 47 (2020).
pubmed: 32300099 pmcid: 7162942 doi: 10.1038/s41392-020-0147-5
Lin, H., Su, X. & He, B. Protein lysine acylation and cysteine succination by intermediates of energy metabolism. ACS Chem. Biol. 7, 947–960 (2012).
pubmed: 22571489 pmcid: 3376250 doi: 10.1021/cb3001793
Zhou, F. et al. ARHGEF3 regulates the stability of ACLY to promote the proliferation of lung cancer. Cell Death Dis. 13, 870 (2022).
pubmed: 36241648 pmcid: 9568610 doi: 10.1038/s41419-022-05297-4
Zhong, Y. et al. The HDAC10 instructs macrophage M2 program via deacetylation of STAT3 and promotes allergic airway inflammation. Theranostics 13, 3568–3581 (2023).
pubmed: 37441601 pmcid: 10334828 doi: 10.7150/thno.82535
Zhao, L., Zhao, J., Zhong, K., Tong, A. & Jia, D. Targeted protein degradation: mechanisms, strategies and application. Signal Transduct. Target. Ther. 7, 113 (2022).
pubmed: 35379777 pmcid: 8977435 doi: 10.1038/s41392-022-00966-4
Witt, O., Deubzer, H. E., Milde, T. & Oehme, I. HDAC family: what are the cancer relevant targets? Cancer Lett. 277, 8–21 (2009).
pubmed: 18824292 doi: 10.1016/j.canlet.2008.08.016
Swatek, K. N. & Komander, D. Ubiquitin modifications. Cell Res. 26, 399–422 (2016).
pubmed: 27012465 pmcid: 4822133 doi: 10.1038/cr.2016.39
Lee, B. H. et al. USP14 deubiquitinates proteasome-bound substrates that are ubiquitinated at multiple sites. Nature 532, 398–401 (2016).
pubmed: 27074503 pmcid: 4844788 doi: 10.1038/nature17433
McClurg, U. L. & Robson, C. N. Deubiquitinating enzymes as oncotargets. Oncotarget 6, 9657–9668 (2015).
pubmed: 25962961 pmcid: 4496387 doi: 10.18632/oncotarget.3922
Wang, F., Ning, S., Yu, B. & Wang, Y. USP14: structure, function, and target inhibition. Front. Pharmacol. 12, 801328 (2021).
pubmed: 35069211 doi: 10.3389/fphar.2021.801328
Liu, Y. et al. USP14 regulates cell cycle progression through deubiquitinating CDK1 in breast cancer. Acta Biochim. Biophys. Sin. 54, 1610–1618 (2022).
pubmed: 36604147 pmcid: 9827946 doi: 10.3724/abbs.2022160
Liu, B. et al. CyclinB1 deubiquitination by USP14 regulates cell cycle progression in breast cancer. Pathol. Res. Pract. 215, 152592 (2019).
pubmed: 31474315 doi: 10.1016/j.prp.2019.152592
Chau, V. et al. A multiubiquitin chain is confined to specific lysine in a targeted short-lived protein. Science 243, 1576–1583 (1989).
pubmed: 2538923 doi: 10.1126/science.2538923
Zhao, C. et al. A self-amplifying USP14-TAZ loop drives the progression and liver metastasis of pancreatic ductal adenocarcinoma. Cell Death Differ. 30, 1–15 (2023).
pubmed: 35906484 doi: 10.1038/s41418-022-01040-w
Yang, X., Li, C. & Chen, Y. Phosphoserine aminotransferase 1: a metabolic enzyme target of cancers. Curr. Cancer Drug Targets 23, 171–186 (2023).
pubmed: 36043756 doi: 10.2174/1568009622666220829105300
Maddocks, O. D. et al. Serine starvation induces stress and p53-dependent metabolic remodelling in cancer cells. Nature 493, 542–546 (2013).
pubmed: 23242140 doi: 10.1038/nature11743
Rose, M. C., Kostyanovskaya, E. & Huang, R. S. Pharmacogenomics of cisplatin sensitivity in non-small cell lung cancer. Genom. Proteom. Bioinform. 12, 198–209 (2014).
doi: 10.1016/j.gpb.2014.10.003
Zhang, C. C. et al. Chemotherapeutic paclitaxel and cisplatin differentially induce pyroptosis in A549 lung cancer cells via caspase-3/GSDME activation. Apoptosis 24, 312–325 (2019).
pubmed: 30710195 doi: 10.1007/s10495-019-01515-1
Zhou, X., Tian, C., Cao, Y., Zhao, M. & Wang, K. The role of serine metabolism in lung cancer: From oncogenesis to tumor treatment. Front. Genet. 13, 1084609 (2022).
pubmed: 36699468 doi: 10.3389/fgene.2022.1084609
Jain, M. et al. Metabolite profiling identifies a key role for glycine in rapid cancer cell proliferation. Science 336, 1040–1044 (2012).
pubmed: 22628656 pmcid: 3526189 doi: 10.1126/science.1218595
Metcalf, S. et al. Selective loss of phosphoserine aminotransferase 1 (PSAT1) suppresses migration, invasion, and experimental metastasis in triple negative breast cancer. Clin. Exp. Metastasis 37, 187–197 (2020).
pubmed: 31630284 doi: 10.1007/s10585-019-10000-7
Feng, M. et al. An integrated pan-cancer analysis of PSAT1: A potential biomarker for survival and immunotherapy. Front. Genet. 13, 975381 (2022).
pubmed: 36105075 pmcid: 9465327 doi: 10.3389/fgene.2022.975381
Yang, Y. et al. PSAT1 regulates cyclin D1 degradation and sustains proliferation of non-small cell lung cancer cells. Int. J. Cancer 136, E39–E50 (2015).
pubmed: 25142862 doi: 10.1002/ijc.29150
Biyik-Sit, R. et al. Nuclear pyruvate kinase M2 (PKM2) contributes to phosphoserine aminotransferase 1 (PSAT1)-mediated cell migration in EGFR-activated lung cancer cells. Cancers 13, 3938 (2021).
pubmed: 34439090 pmcid: 8391706 doi: 10.3390/cancers13163938
Jin, H. O. et al. Knock-down of PSAT1 enhances sensitivity of NSCLC cells to glutamine-limiting conditions. Anticancer Res. 39, 6723–6730 (2019).
pubmed: 31810937 doi: 10.21873/anticanres.13887
Zhao, S. et al. Regulation of cellular metabolism by protein lysine acetylation. Science 327, 1000–1004 (2010).
pubmed: 20167786 pmcid: 3232675 doi: 10.1126/science.1179689
Shahbazian, M. D. & Grunstein, M. Functions of site-specific histone acetylation and deacetylation. Annu. Rev. Biochem. 76, 75–100 (2007).
pubmed: 17362198 doi: 10.1146/annurev.biochem.76.052705.162114
Ho, T. C. S., Chan, A. H. Y. & Ganesan, A. Thirty years of HDAC inhibitors: 2020 insight and hindsight. J. Med. Chem. 63, 12460–12484 (2020).
pubmed: 32608981 doi: 10.1021/acs.jmedchem.0c00830
Lei, Y. et al. Hdac7 promotes lung tumorigenesis by inhibiting Stat3 activation. Mol. Cancer 16, 170 (2017).
pubmed: 29126425 pmcid: 5681774 doi: 10.1186/s12943-017-0736-2
Wei, Y. et al. Endothelial progenitor cells contribute to neovascularization of non-small cell lung cancer via histone deacetylase 7-mediated cytoskeleton regulation and angiogenic genes transcription. Int. J. Cancer 143, 657–667 (2018).
pubmed: 29490434 doi: 10.1002/ijc.31349
Hussain, S., Zhang, Y. & Galardy, P. J. DUBs and cancer: the role of deubiquitinating enzymes as oncogenes, non-oncogenes and tumor suppressors. Cell Cycle 8, 1688–1697 (2009).
pubmed: 19448430 doi: 10.4161/cc.8.11.8739
Hu, M. et al. Structure and mechanisms of the proteasome-associated deubiquitinating enzyme USP14. EMBO J. 24, 3747–3756 (2005).
pubmed: 16211010 pmcid: 1276716 doi: 10.1038/sj.emboj.7600832

Auteurs

Yuhan Liu (Y)

Jiangxi Provincial Key Laboratory of Respirtory Diseases, Jiangxi Institute of Respiratory Disease, The Department of Respiratory and Critical Care Medicine, The First Affiliated Hospital, Jiangxi Medical College, Nanchang University, Nanchang, Jiangxi, China.
School of Basic Medical Sciences, Jiangxi Medical College, Nanchang University, Nanchang, Jiangxi, China.
Department of Thoracic Surgery, The First Affiliated Hospital, Jiangxi Medical College, Nanchang University, Nanchang, Jiangxi, China.

Wenze Xun (W)

School of Basic Medical Sciences, Jiangxi Medical College, Nanchang University, Nanchang, Jiangxi, China.

Tao Zhao (T)

School of Basic Medical Sciences, Jiangxi Medical College, Nanchang University, Nanchang, Jiangxi, China.

Menglin Huang (M)

School of Basic Medical Sciences, Jiangxi Medical College, Nanchang University, Nanchang, Jiangxi, China.

Longhua Sun (L)

Jiangxi Provincial Key Laboratory of Respirtory Diseases, Jiangxi Institute of Respiratory Disease, The Department of Respiratory and Critical Care Medicine, The First Affiliated Hospital, Jiangxi Medical College, Nanchang University, Nanchang, Jiangxi, China.
Jiangxi Clinical Research Center for Respiratory Diseases, Nanchang, Jiangxi, China.
China-Japan Friendship Jiangxi Hospital, National Regional Center for Respiratory Medicine, Nanchang, Jiangxi, China.

Guilan Wen (G)

Jiangxi Provincial Key Laboratory of Respirtory Diseases, Jiangxi Institute of Respiratory Disease, The Department of Respiratory and Critical Care Medicine, The First Affiliated Hospital, Jiangxi Medical College, Nanchang University, Nanchang, Jiangxi, China.

Xiuhua Kang (X)

Jiangxi Provincial Key Laboratory of Respirtory Diseases, Jiangxi Institute of Respiratory Disease, The Department of Respiratory and Critical Care Medicine, The First Affiliated Hospital, Jiangxi Medical College, Nanchang University, Nanchang, Jiangxi, China.

Jianbin Wang (J)

School of Basic Medical Sciences, Jiangxi Medical College, Nanchang University, Nanchang, Jiangxi, China. jianbinwang@ncu.edu.cn.
Department of Thoracic Surgery, The First Affiliated Hospital, Jiangxi Medical College, Nanchang University, Nanchang, Jiangxi, China. jianbinwang@ncu.edu.cn.
The MOE Basic Research and Innovation Center for the Targeted Therapeutics of Solid Tumors, Jiangxi Medical College, Nanchang University, Nanchang, Jiangxi, China. jianbinwang@ncu.edu.cn.

Tianyu Han (T)

Jiangxi Provincial Key Laboratory of Respirtory Diseases, Jiangxi Institute of Respiratory Disease, The Department of Respiratory and Critical Care Medicine, The First Affiliated Hospital, Jiangxi Medical College, Nanchang University, Nanchang, Jiangxi, China. hantianyu87@163.com.
Jiangxi Clinical Research Center for Respiratory Diseases, Nanchang, Jiangxi, China. hantianyu87@163.com.
China-Japan Friendship Jiangxi Hospital, National Regional Center for Respiratory Medicine, Nanchang, Jiangxi, China. hantianyu87@163.com.
The MOE Basic Research and Innovation Center for the Targeted Therapeutics of Solid Tumors, Jiangxi Medical College, Nanchang University, Nanchang, Jiangxi, China. hantianyu87@163.com.

Articles similaires

[Redispensing of expensive oral anticancer medicines: a practical application].

Lisanne N van Merendonk, Kübra Akgöl, Bastiaan Nuijen
1.00
Humans Antineoplastic Agents Administration, Oral Drug Costs Counterfeit Drugs

Smoking Cessation and Incident Cardiovascular Disease.

Jun Hwan Cho, Seung Yong Shin, Hoseob Kim et al.
1.00
Humans Male Smoking Cessation Cardiovascular Diseases Female
Humans United States Aged Cross-Sectional Studies Medicare Part C
1.00
Humans Yoga Low Back Pain Female Male

Classifications MeSH