دورية أكاديمية
أعرض في EDS

UBQLN1 links proteostasis and mitochondria function to telomere maintenance in human embryonic stem cells.

التفاصيل البيبلوغرافية
العنوان: UBQLN1 links proteostasis and mitochondria function to telomere maintenance in human embryonic stem cells.
المؤلفون: Zhao S; State Key Laboratory of Medicinal Chemical Biology, Nankai University, Tianjin, 300350, China.; Frontiers Science Center for Cell Responses, College of Life Science, Nankai University, Tianjin, 300071, China., Li J; State Key Laboratory of Medicinal Chemical Biology, Nankai University, Tianjin, 300350, China.; Frontiers Science Center for Cell Responses, College of Life Science, Nankai University, Tianjin, 300071, China., Duan S; Frontiers Science Center for Cell Responses, College of Life Science, Nankai University, Tianjin, 300071, China., Liu C; State Key Laboratory of Medicinal Chemical Biology, Nankai University, Tianjin, 300350, China.; Frontiers Science Center for Cell Responses, College of Life Science, Nankai University, Tianjin, 300071, China., Wang H; State Key Laboratory of Medicinal Chemical Biology, Nankai University, Tianjin, 300350, China.; Frontiers Science Center for Cell Responses, College of Life Science, Nankai University, Tianjin, 300071, China., Lu J; State Key Laboratory of Medicinal Chemical Biology, Nankai University, Tianjin, 300350, China.; Frontiers Science Center for Cell Responses, College of Life Science, Nankai University, Tianjin, 300071, China., Zhao N; State Key Laboratory of Medicinal Chemical Biology, Nankai University, Tianjin, 300350, China.; Frontiers Science Center for Cell Responses, College of Life Science, Nankai University, Tianjin, 300071, China., Sheng X; Experimental Animal Center, Nankai University, Tianjin, 300350, China., Wu Y; State Key Laboratory of Medicinal Chemical Biology, Nankai University, Tianjin, 300350, China.; Frontiers Science Center for Cell Responses, College of Life Science, Nankai University, Tianjin, 300071, China., Li Y; Frontiers Science Center for Cell Responses, College of Life Science, Nankai University, Tianjin, 300071, China., Sun B; State Key Laboratory of Medicinal Chemical Biology, Nankai University, Tianjin, 300350, China.; Frontiers Science Center for Cell Responses, College of Life Science, Nankai University, Tianjin, 300071, China., Liu L; State Key Laboratory of Medicinal Chemical Biology, Nankai University, Tianjin, 300350, China. liulin@nankai.edu.cn.; Frontiers Science Center for Cell Responses, College of Life Science, Nankai University, Tianjin, 300071, China. liulin@nankai.edu.cn.; Experimental Animal Center, Nankai University, Tianjin, 300350, China. liulin@nankai.edu.cn.; Tianjin Union Medical Center, Nankai University, Tianjin, 300071, China. liulin@nankai.edu.cn.
المصدر: Stem cell research & therapy [Stem Cell Res Ther] 2024 Jun 21; Vol. 15 (1), pp. 180. Date of Electronic Publication: 2024 Jun 21.
نوع المنشور: Journal Article
اللغة: English
بيانات الدورية: Publisher: BioMed Central Country of Publication: England NLM ID: 101527581 Publication Model: Electronic Cited Medium: Internet ISSN: 1757-6512 (Electronic) Linking ISSN: 17576512 NLM ISO Abbreviation: Stem Cell Res Ther Subsets: MEDLINE
أسماء مطبوعة: Original Publication: London : BioMed Central
مواضيع طبية MeSH: Human Embryonic Stem Cells*/metabolism , Human Embryonic Stem Cells*/cytology , Autophagy-Related Proteins*/metabolism , Autophagy-Related Proteins*/genetics , Mitochondria*/metabolism , Proteostasis* , Telomere*/metabolism , Telomere Homeostasis*, Humans ; Adaptor Proteins, Signal Transducing/metabolism ; Adaptor Proteins, Signal Transducing/genetics ; Cell Cycle Proteins/metabolism ; Cell Cycle Proteins/genetics ; Oxidative Stress ; DNA Damage
مستخلص: Background: Telomeres consist of repetitive DNA sequences at the chromosome ends to protect chromosomal stability, and primarily maintained by telomerase or occasionally by alternative telomere lengthening of telomeres (ALT) through recombination-based mechanisms. Additional mechanisms that may regulate telomere maintenance remain to be explored. Simultaneous measurement of telomere length and transcriptome in the same human embryonic stem cell (hESC) revealed that mRNA expression levels of UBQLN1 exhibit linear relationship with telomere length.
Methods: In this study, we first generated UBQLN1-deficient hESCs and compared with the wild-type (WT) hESCs the telomere length and molecular change at RNA and protein level by RNA-seq and proteomics. Then we identified the potential interacting proteins with UBQLN1 using immunoprecipitation-mass spectrometry (IP-MS). Furthermore, the potential mechanisms underlying the shortened telomeres in UBQLN1-deficient hESCs were analyzed.
Results: We show that Ubiquilin1 (UBQLN1) is critical for telomere maintenance in human embryonic stem cells (hESCs) via promoting mitochondrial function. UBQLN1 deficiency leads to oxidative stress, loss of proteostasis, mitochondria dysfunction, DNA damage, and telomere attrition. Reducing oxidative damage and promoting mitochondria function by culture under hypoxia condition or supplementation with N-acetylcysteine partly attenuate the telomere attrition induced by UBQLN1 deficiency. Moreover, UBQLN1 deficiency/telomere shortening downregulates genes for neuro-ectoderm lineage differentiation.
Conclusions: Altogether, UBQLN1 functions to scavenge ubiquitinated proteins, preventing their overloading mitochondria and elevated mitophagy. UBQLN1 maintains mitochondria and telomeres by regulating proteostasis and plays critical role in neuro-ectoderm differentiation.
(© 2024. The Author(s).)
References: Nat Cell Biol. 2021 Dec;23(12):1271-1286. (PMID: 34873283)
Cell. 2021 Jan 21;184(2):306-322. (PMID: 33450206)
Biochem Soc Trans. 2010 Feb;38(Pt 1):150-5. (PMID: 20074050)
Stem Cells. 2016 Oct;34(10):2471-2484. (PMID: 27299710)
EMBO J. 2019 Feb 1;38(3):. (PMID: 30591555)
Neuroscience. 2007 Apr 14;145(4):1348-58. (PMID: 17055653)
Ann Clin Lab Sci. 2016 May;46(3):260-5. (PMID: 27312549)
Sci Rep. 2021 Feb 10;11(1):3490. (PMID: 33568707)
Bioinformatics. 2014 Apr 1;30(7):923-30. (PMID: 24227677)
BMC Biol. 2017 Dec 08;15(1):114. (PMID: 29216888)
Aging Cell. 2002 Oct;1(1):40-6. (PMID: 12882352)
Proc Natl Acad Sci U S A. 2019 Sep 10;116(37):18435-18444. (PMID: 31451640)
Cell. 2013 Jun 6;153(6):1194-217. (PMID: 23746838)
Innovation (Camb). 2021 Jul 01;2(3):100141. (PMID: 34557778)
Protein Cell. 2019 Sep;10(9):668-680. (PMID: 31152430)
Curr Microbiol. 2020 May;77(5):695-701. (PMID: 31263924)
Arthritis Rheum. 2012 Sep;64(9):2937-46. (PMID: 22549432)
Aging (Albany NY). 2020 Dec 15;13(2):2089-2100. (PMID: 33323554)
EMBO J. 2016 Mar 15;35(6):618-34. (PMID: 26903601)
Nat Protoc. 2009;4(1):44-57. (PMID: 19131956)
Neurology. 2001 Oct 23;57(8):1515-7. (PMID: 11673605)
Cell Mol Life Sci. 2016 Sep;73(18):3497-506. (PMID: 27137187)
Dev Cell. 2014 Apr 14;29(1):7-19. (PMID: 24735877)
FEBS Lett. 1997 Jul 7;411(1):77-82. (PMID: 9247146)
Neoplasia. 2013 Nov;15(11):1301-13. (PMID: 24339742)
Biogerontology. 2024 Apr;25(2):289-300. (PMID: 37864609)
Cell Stress. 2019 Mar 15;3(4):110-114. (PMID: 31225505)
J Neurochem. 2012 Feb;120(3):419-29. (PMID: 22077634)
J Cell Biochem. 2017 Aug;118(8):2261-2270. (PMID: 28075048)
Genome Biol. 2014;15(12):550. (PMID: 25516281)
Nucleic Acids Res. 2002 May 15;30(10):e47. (PMID: 12000852)
PLoS Genet. 2023 Jul 18;19(7):e1010856. (PMID: 37463174)
Cell Death Dis. 2012 Nov 22;3:e430. (PMID: 23171850)
Genes Dev. 2014 Sep 1;28(17):1885-99. (PMID: 25128433)
Nat Biotechnol. 2019 Aug;37(8):907-915. (PMID: 31375807)
Nat Struct Mol Biol. 2017 Jan;24(1):30-39. (PMID: 27918544)
J Cell Biol. 2017 Oct 2;216(10):3231-3247. (PMID: 28893839)
J Immunol Methods. 2001 May 1;251(1-2):81-91. (PMID: 11292484)
Proteomics. 2011 Nov;11(21):4243-56. (PMID: 21954051)
Elife. 2017 Sep 21;6:. (PMID: 28933694)
Biochim Biophys Acta. 1999 Feb 9;1410(2):103-23. (PMID: 10076021)
Trends Biochem Sci. 2002 Jul;27(7):339-44. (PMID: 12114022)
Neurobiol Aging. 2003 Jan-Feb;24(1):77-84. (PMID: 12493553)
Mol Cell. 2016 Jul 7;63(1):21-33. (PMID: 27345149)
Cell Death Differ. 2021 Feb;28(2):570-590. (PMID: 33414510)
Semin Cell Dev Biol. 2019 Sep;93:111-124. (PMID: 30278225)
Biochim Biophys Acta Gen Subj. 2019 Oct;1863(10):1568-1574. (PMID: 31175912)
Trends Cell Biol. 2000 Dec;10(12):524-30. (PMID: 11121744)
Methods Mol Biol. 2015;1239:197-217. (PMID: 25408407)
PLoS Pathog. 2020 Feb 24;16(2):e1008105. (PMID: 32092124)
Proteomics. 2017 Mar;17(6):. (PMID: 28044432)
Mol Cell Proteomics. 2011 May;10(5):M110.003756. (PMID: 21048196)
N Engl J Med. 2005 Mar 3;352(9):884-94. (PMID: 15745979)
Proc Natl Acad Sci U S A. 2005 Oct 25;102(43):15545-50. (PMID: 16199517)
Exp Gerontol. 2005 Jun;40(6):466-72. (PMID: 15963673)
Nat Struct Mol Biol. 2015 Nov;22(11):848-52. (PMID: 26581518)
J Neurosci. 2014 Feb 19;34(8):2813-21. (PMID: 24553923)
Autophagy. 2023 Feb;19(2):724-725. (PMID: 35939345)
Dev Biol. 2000 Nov 15;227(2):271-8. (PMID: 11071754)
Cell Calcium. 2014 Dec;56(6):446-56. (PMID: 25266962)
Nat Protoc. 2016 Dec;11(12):2301-2319. (PMID: 27809316)
Protein Cell. 2019 Sep;10(9):649-667. (PMID: 30796637)
Methods Mol Biol. 2019;1999:327-333. (PMID: 31127589)
Neurobiol Aging. 2021 Nov;107:153-158. (PMID: 34172279)
Protein Cell. 2020 Jan;11(1):60-70. (PMID: 31350723)
Am J Med Genet B Neuropsychiatr Genet. 2017 Dec;174(8):772-778. (PMID: 28856789)
J Cell Sci. 2014 Feb 15;127(Pt 4):752-62. (PMID: 24338368)
Neurobiol Dis. 2012 Mar;45(3):1111-20. (PMID: 22227002)
Blood. 2022 Aug 11;140(6):608-618. (PMID: 35421215)
Stem Cells. 2008 Apr;26(4):850-63. (PMID: 18203676)
FASEB J. 2010 Aug;24(8):2702-15. (PMID: 20354136)
Curr Biol. 2012 Jan 24;22(2):135-41. (PMID: 22226745)
Nat Rev Neurol. 2019 Oct;15(10):565-581. (PMID: 31501588)
Differentiation. 2018 Jan - Feb;99:21-27. (PMID: 29274896)
Nat Protoc. 2006;1(5):2365-76. (PMID: 17406480)
Mutat Res. 2012 Feb 1;730(1-2):28-36. (PMID: 21575645)
Cell. 2012 Aug 3;150(3):481-94. (PMID: 22863003)
J Photochem Photobiol B. 1991 Apr;9(1):105-16. (PMID: 1907641)
Mol Neurobiol. 2020 Feb;57(2):937-948. (PMID: 31620993)
Mol Cell. 2019 Jul 11;75(1):117-130.e6. (PMID: 31101499)
Nat Commun. 2016 Jul 13;7:12170. (PMID: 27405751)
Biomolecules. 2020 May 21;10(5):. (PMID: 32455657)
Cell Res. 2011 May;21(5):779-92. (PMID: 21283131)
Nat Protoc. 2006;1(3):1583-90. (PMID: 17406450)
EMBO J. 1992 May;11(5):1921-9. (PMID: 1582420)
معلومات مُعتمدة: 32030033 National Natural Science Foundation of China; 82230052 National Natural Science Foundation of China; 32261160571 National Natural Science Foundation of China; 20JCZDJC00550 Tianjin Science and Technology Plan Key Project
فهرسة مساهمة: Keywords: Mitochondria; Proteostasis; Telomere; UBQLN1; Ubiquitin-proteasome; hESC differentiation
المشرفين على المادة: 0 (Autophagy-Related Proteins)
0 (UBQLN1 protein, human)
0 (Adaptor Proteins, Signal Transducing)
0 (Cell Cycle Proteins)
تواريخ الأحداث: Date Created: 20240620 Date Completed: 20240621 Latest Revision: 20240623
رمز التحديث: 20240623
مُعرف محوري في PubMed: PMC11191273
DOI: 10.1186/s13287-024-03789-y
PMID: 38902824
قاعدة البيانات: MEDLINE
الوصف
تدمد:1757-6512
DOI:10.1186/s13287-024-03789-y