Emerging Role of UFMylation in Secretory Cells Involved in the Endocrine System by Maintaining ER Proteostasis

Overview

Journal Front Endocrinol (Lausanne)

Specialty Endocrinology

Date 2023 Feb 6

PMID 36743909

Authors

Yun Cheng

Zikang Niu

Yafei Cai

Wei Zhang

Affiliations

Soon will be listed here.

Abstract

Ubiquitin-fold modifier 1 (UFM1) is a ubiquitin-like molecule (UBL) discovered almost two decades ago, but our knowledge about the cellular and molecular mechanisms of this novel protein post-translational modification is still very fragmentary. In this review, we first summarize the core enzymes and factors involved in the UFMylation cascade, which, similar to ubiquitin, is consecutively catalyzed by UFM1-activating enzyme 5 (UBA5), UFM1-conjugating enzyme 1 (UFC1) and UFM1-specific ligase 1 (UFL1). Inspired by the substantial implications of UFM1 machinery in the secretory pathway, we next concentrate on the puzzling role of UFMylation in maintaining ER protein homeostasis, intending to illustrate the underlying mechanisms and future perspectives. At last, given a robust ER network is a hallmark of healthy endocrine secretory cells, we emphasize the function of UFM1 modification in physiology and pathology in the context of endocrine glands pancreas and female ovaries, aiming to provide precise insight into other internal glands of the endocrine system.

Citing Articles

Eg5 UFMylation promotes spindle organization during mitosis.

Li G, Huang Y, Han W, Wei L, Huang H, Zhu Y Cell Death Dis. 2024; 15(7):544.

PMID: 39085203 PMC: 11291904. DOI: 10.1038/s41419-024-06934-w.

Patient derived model of -associated encephalopathy identifies defects in neurodevelopment and highlights potential therapies.

Chen H, Wang Y, Blan A, Almanza-Fuerte E, Bonkowski E, Bajpai R bioRxiv. 2024; .

PMID: 38328212 PMC: 10849720. DOI: 10.1101/2024.01.25.577254.

A neuroprotective role of Ufmylation through Atg9 in the aging brain of Drosophila.

Li H, Yu Z, Niu Z, Cheng Y, Wei Z, Cai Y Cell Mol Life Sci. 2023; 80(5):129.

PMID: 37086384 PMC: 11073442. DOI: 10.1007/s00018-023-04778-9.

References

Acosta-Alvear D, Zhou Y, Blais A, Tsikitis M, Lents N, Arias C . XBP1 controls diverse cell type- and condition-specific transcriptional regulatory networks. Mol Cell. 2007; 27(1):53-66. DOI: 10.1016/j.molcel.2007.06.011. View

Varshavsky A . The Ubiquitin System, Autophagy, and Regulated Protein Degradation. Annu Rev Biochem. 2017; 86:123-128. DOI: 10.1146/annurev-biochem-061516-044859. View

Wei Y, Xu X . UFMylation: A Unique & Fashionable Modification for Life. Genomics Proteomics Bioinformatics. 2016; 14(3):140-146. PMC: 4936604. DOI: 10.1016/j.gpb.2016.04.001. View

Liu Y, Sowell S, Luo Y, Chaubey A, Cameron R, Kim H . Autism and Intellectual Disability-Associated KIRREL3 Interacts with Neuronal Proteins MAP1B and MYO16 with Potential Roles in Neurodevelopment. PLoS One. 2015; 10(4):e0123106. PMC: 4406691. DOI: 10.1371/journal.pone.0123106. View

Xi P, Ding D, Zhou J, Wang M, Cong Y . DDRGK1 regulates NF-κB activity by modulating IκBα stability. PLoS One. 2013; 8(5):e64231. PMC: 3651127. DOI: 10.1371/journal.pone.0064231. View

Nishitoh H, Matsuzawa A, Tobiume K, Saegusa K, Takeda K, Inoue K . ASK1 is essential for endoplasmic reticulum stress-induced neuronal cell death triggered by expanded polyglutamine repeats. Genes Dev. 2002; 16(11):1345-55. PMC: 186318. DOI: 10.1101/gad.992302. View

Li J, Johnson J, Su H . Ubiquitin and Ubiquitin-like proteins in cardiac disease and protection. Curr Drug Targets. 2015; 19(9):989-1002. PMC: 4899309. DOI: 10.2174/1389450117666151209114608. View

Zhang J, Liang Y, Lin Y, Liu Y, YouYou , Yin W . IRE1α-TRAF2-ASK1 pathway is involved in CSTMP-induced apoptosis and ER stress in human non-small cell lung cancer A549 cells. Biomed Pharmacother. 2016; 82:281-9. DOI: 10.1016/j.biopha.2016.04.050. View

Cabrera-Serrano M, Coote D, Azmanov D, Goullee H, Andersen E, McLean C . A homozygous pathogenic variant causes a fatal congenital neuropathy. J Med Genet. 2020; 57(12):835-842. DOI: 10.1136/jmedgenet-2019-106496. View

10.

Pick E, Hofmann K, Glickman M . PCI complexes: Beyond the proteasome, CSN, and eIF3 Troika. Mol Cell. 2009; 35(3):260-4. DOI: 10.1016/j.molcel.2009.07.009. View

11.

Colin E, Daniel J, Ziegler A, Wakim J, Scrivo A, Haack T . Biallelic Variants in UBA5 Reveal that Disruption of the UFM1 Cascade Can Result in Early-Onset Encephalopathy. Am J Hum Genet. 2016; 99(3):695-703. PMC: 5011045. DOI: 10.1016/j.ajhg.2016.06.030. View

12.

Zhou J . Two potential molecular signaling pathways of the UFL1 gene to induce the endoplasmic reticulum stress and apoptosis of the ovarian granulosa cell. Med Hypotheses. 2020; 145:110328. DOI: 10.1016/j.mehy.2020.110328. View

13.

Chen L, Chao C, Chen C, Lee Y, Chen Y, Shiue Y . Expression of 25 high egg production related transcripts that identified from hypothalamus and pituitary gland in red-feather Taiwan country chickens. Anim Reprod Sci. 2006; 100(1-2):172-85. DOI: 10.1016/j.anireprosci.2006.07.005. View

14.

Cai Y, Pi W, Sivaprakasam S, Zhu X, Zhang M, Chen J . UFBP1, a Key Component of the Ufm1 Conjugation System, Is Essential for Ufmylation-Mediated Regulation of Erythroid Development. PLoS Genet. 2015; 11(11):e1005643. PMC: 4636156. DOI: 10.1371/journal.pgen.1005643. View

15.

Jing Y, Mao Z, Chen F . UFMylation System: An Emerging Player in Tumorigenesis. Cancers (Basel). 2022; 14(14). PMC: 9323365. DOI: 10.3390/cancers14143501. View

16.

Schuren A, Boer I, Bouma E, Van de Weijer M, Costa A, Hubel P . The UFM1 Pathway Impacts HCMV US2-Mediated Degradation of HLA Class I. Molecules. 2021; 26(2). PMC: 7827699. DOI: 10.3390/molecules26020287. View

17.

Liu J, Wang Y, Song L, Zeng L, Yi W, Liu T . A critical role of DDRGK1 in endoplasmic reticulum homoeostasis via regulation of IRE1α stability. Nat Commun. 2017; 8:14186. PMC: 5290148. DOI: 10.1038/ncomms14186. View

18.

Wang Z, Gong Y, Peng B, Shi R, Fan D, Zhao H . MRE11 UFMylation promotes ATM activation. Nucleic Acids Res. 2019; 47(8):4124-4135. PMC: 6486557. DOI: 10.1093/nar/gkz110. View

19.

Kwon J, Cho H, Han S, No J, Kwon J, Kim H . A novel LZAP-binding protein, NLBP, inhibits cell invasion. J Biol Chem. 2010; 285(16):12232-40. PMC: 2852962. DOI: 10.1074/jbc.M109.065920. View

20.

Yang R, Wang H, Kang B, Chen B, Shi Y, Yang S . CDK5RAP3, a UFL1 substrate adaptor, is crucial for liver development. Development. 2019; 146(2). DOI: 10.1242/dev.169235. View