{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,23]],"date-time":"2026-07-23T11:43:15Z","timestamp":1784806995436,"version":"3.55.0"},"reference-count":77,"publisher":"Wiley","issue":"10","license":[{"start":{"date-parts":[[2020,8,22]],"date-time":"2020-08-22T00:00:00Z","timestamp":1598054400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Aging Cell"],"published-print":{"date-parts":[[2020,10]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Sumoylation is one of the key regulatory mechanisms in eukaryotes. Our previous studies reveal that sumoylation plays indispensable roles during lens differentiation (Yan et al. 2010. <jats:italic>Proc Natl Acad Sci USA<\/jats:italic>. 107:21034\u201321039; Gong et al. 2014. <jats:italic>Proc Natl Acad Sci USA<\/jats:italic>. 111:5574\u20135579). Whether sumoylation is implicated in cataractogenesis, a disease largely derived from aging, remains elusive. In the present study, we have examined the changing patterns of the sumoylation ligases and de\u2010sumoylation enzymes (SENPs) and their substrates including Pax6 and other proteins in cataractous lenses of different age groups from 50 to 90\u00a0years old. It is found that compared with normal lenses, sumoylation ligases 1 and 3, de\u2010sumoylation enzymes SENP3\/7\/8, and p46 Pax6 are clearly increased. In contrast, Ubc9 is significantly decreased. Among different cataract patients from 50s to 70s, male patients express more sumoylation enzymes and p46 Pax6. Ubc9 and SENP6 display age\u2010dependent increase. The p46 Pax6 displays age\u2010dependent decrease in normal lens, remains relatively stable in senile cataracts but becomes di\u2010sumoylated in complicated cataracts. In contrast, sumoylation of p32 Pax6 is observed in senile cataracts and increases its stability. Treatment of rat lenses with oxidative stress increases Pax6 expression without sumoylation but promotes apoptosis. Thus, our results show that the changing patterns in Ubc9, SENP6, and Pax6 levels can act as molecular markers for senile cataract and the di\u2010sumoylated p46 Pax6 for complicated cataract. Together, our results reveal the presence of molecular signature for both senile and complicated cataracts. Moreover, our study indicates that sumoylation is implicated in control of aging and cataractogenesis.<\/jats:p>","DOI":"10.1111\/acel.13222","type":"journal-article","created":{"date-parts":[[2020,8,22]],"date-time":"2020-08-22T16:05:39Z","timestamp":1598112339000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":15,"title":["Molecular signature for senile and complicated cataracts derived from analysis of sumoylation enzymes and their substrates in human cataract lenses"],"prefix":"10.1111","volume":"19","author":[{"given":"Fang\u2010Yuan","family":"Liu","sequence":"first","affiliation":[{"name":"State Key Laboratory of Ophthalmology Zhongshan Ophthalmic Center Sun Yat\u2010Sen University Guangzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jia\u2010Ling","family":"Fu","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Ophthalmology Zhongshan Ophthalmic Center Sun Yat\u2010Sen University Guangzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ling","family":"Wang","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Ophthalmology Zhongshan Ophthalmic Center Sun Yat\u2010Sen University Guangzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qian","family":"Nie","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Ophthalmology Zhongshan Ophthalmic Center Sun Yat\u2010Sen University Guangzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhongwen","family":"Luo","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Ophthalmology Zhongshan Ophthalmic Center Sun Yat\u2010Sen University Guangzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Min","family":"Hou","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Ophthalmology Zhongshan Ophthalmic Center Sun Yat\u2010Sen University Guangzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuan","family":"Yang","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Ophthalmology Zhongshan Ophthalmic Center Sun Yat\u2010Sen University Guangzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiao\u2010Dong","family":"Gong","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Ophthalmology Zhongshan Ophthalmic Center Sun Yat\u2010Sen University Guangzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yan","family":"Wang","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Ophthalmology Zhongshan Ophthalmic Center Sun Yat\u2010Sen University Guangzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuan","family":"Xiao","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Ophthalmology Zhongshan Ophthalmic Center Sun Yat\u2010Sen University Guangzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiawen","family":"Xiang","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Ophthalmology Zhongshan Ophthalmic Center Sun Yat\u2010Sen University Guangzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xuebin","family":"Hu","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Ophthalmology Zhongshan Ophthalmic Center Sun Yat\u2010Sen University Guangzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lan","family":"Zhang","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Ophthalmology Zhongshan Ophthalmic Center Sun Yat\u2010Sen University Guangzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mingxing","family":"Wu","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Ophthalmology Zhongshan Ophthalmic Center Sun Yat\u2010Sen University Guangzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Weirong","family":"Chen","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Ophthalmology Zhongshan Ophthalmic Center Sun Yat\u2010Sen University Guangzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bing","family":"Cheng","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Ophthalmology Zhongshan Ophthalmic Center Sun Yat\u2010Sen University Guangzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lixia","family":"Luo","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Ophthalmology Zhongshan Ophthalmic Center Sun Yat\u2010Sen University Guangzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xinyu","family":"Zhang","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Ophthalmology Zhongshan Ophthalmic Center Sun Yat\u2010Sen University Guangzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xialin","family":"Liu","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Ophthalmology Zhongshan Ophthalmic Center Sun Yat\u2010Sen University Guangzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Danying","family":"Zheng","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Ophthalmology Zhongshan Ophthalmic Center Sun Yat\u2010Sen University Guangzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shengsong","family":"Huang","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Ophthalmology Zhongshan Ophthalmic Center Sun Yat\u2010Sen University Guangzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yizhi","family":"Liu","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Ophthalmology Zhongshan Ophthalmic Center Sun Yat\u2010Sen University Guangzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7398-7630","authenticated-orcid":false,"given":"David Wan\u2010Cheng","family":"Li","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Ophthalmology Zhongshan Ophthalmic Center Sun Yat\u2010Sen University Guangzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2020,8,22]]},"reference":[{"key":"e_1_2_12_2_1","doi-asserted-by":"publisher","DOI":"10.1101\/gad.184000"},{"key":"e_1_2_12_3_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrn2194"},{"key":"e_1_2_12_4_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1800498115"},{"key":"e_1_2_12_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.exer.2016.03.024"},{"key":"e_1_2_12_6_1","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/ddt204"},{"key":"e_1_2_12_7_1","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.neuro.20.1.483"},{"key":"e_1_2_12_8_1","doi-asserted-by":"publisher","DOI":"10.1128\/MCB.13.12.7257"},{"key":"e_1_2_12_9_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M110531200"},{"key":"e_1_2_12_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/0022-1759(93)90011-U"},{"key":"e_1_2_12_11_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.92.10.4681"},{"key":"e_1_2_12_12_1","doi-asserted-by":"publisher","DOI":"10.1101\/gad.7.10.2048"},{"key":"e_1_2_12_13_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature19360"},{"issue":"3","key":"e_1_2_12_14_1","first-page":"581","article-title":"Skewed X\u2010chromosome inactivation in female carriers of dyskeratosis congenita","volume":"60","author":"Devriendt K.","year":"1997","journal-title":"American Journal of Human Genetics"},{"key":"e_1_2_12_15_1","doi-asserted-by":"crossref","first-page":"3173","DOI":"10.1242\/jcs.113.18.3173","article-title":"Overexpression of PAX6(5a) in lens fiber cells results in cataract and upregulation of (alpha)5(beta)1 integrin expression","volume":"113","author":"Duncan M. K.","year":"2000","journal-title":"Journal of Cell Science"},{"key":"e_1_2_12_16_1","doi-asserted-by":"crossref","first-page":"8355","DOI":"10.1016\/S0021-9258(17)37201-0","article-title":"Identification of a Pax paired domain recognition sequence and evidence for DNA\u2010dependent conformational changes","volume":"269","author":"Epstein J.","year":"1994","journal-title":"Journal of Biological Chemistry"},{"key":"e_1_2_12_17_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.exer.2016.06.018"},{"key":"e_1_2_12_18_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM199912023412302"},{"key":"e_1_2_12_19_1","doi-asserted-by":"publisher","DOI":"10.1146\/annurev-biochem-061909-093311"},{"key":"e_1_2_12_20_1","doi-asserted-by":"publisher","DOI":"10.1042\/BCJ20170268"},{"key":"e_1_2_12_21_1","doi-asserted-by":"publisher","DOI":"10.1042\/BCJ20190743"},{"key":"e_1_2_12_22_1","first-page":"107","volume-title":"Abstract Book of the 6th International Conference on the Lens","author":"Fu J. L.","year":"2019"},{"key":"e_1_2_12_23_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrm3011"},{"key":"e_1_2_12_24_1","doi-asserted-by":"publisher","DOI":"10.1016\/0014-4835(90)90113-9"},{"key":"e_1_2_12_25_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrm2293"},{"key":"e_1_2_12_26_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0014-4835(05)80105-8"},{"key":"e_1_2_12_27_1","doi-asserted-by":"publisher","DOI":"10.1038\/ng0894-463"},{"key":"e_1_2_12_28_1","doi-asserted-by":"publisher","DOI":"10.1038\/ng1192-232"},{"key":"e_1_2_12_29_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1315034111"},{"key":"e_1_2_12_30_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1715237115"},{"key":"e_1_2_12_31_1","doi-asserted-by":"publisher","DOI":"10.1101\/gad.378206"},{"key":"e_1_2_12_32_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.7892602"},{"key":"e_1_2_12_33_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrm.2016.81"},{"key":"e_1_2_12_34_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrm3478"},{"key":"e_1_2_12_35_1","doi-asserted-by":"publisher","DOI":"10.1038\/354522a0"},{"key":"e_1_2_12_36_1","doi-asserted-by":"publisher","DOI":"10.1167\/iovs.05-0154"},{"key":"e_1_2_12_37_1","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.biochem.73.011303.074118"},{"key":"e_1_2_12_38_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M507227200"},{"key":"e_1_2_12_39_1","doi-asserted-by":"publisher","DOI":"10.1038\/ncb1415"},{"key":"e_1_2_12_40_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0710343105"},{"key":"e_1_2_12_41_1","doi-asserted-by":"publisher","DOI":"10.3109\/02713689309024624"},{"key":"e_1_2_12_42_1","doi-asserted-by":"publisher","DOI":"10.1242\/jcs.211904"},{"key":"e_1_2_12_43_1","doi-asserted-by":"publisher","DOI":"10.1091\/mbc.e05-01-0010"},{"key":"e_1_2_12_44_1","doi-asserted-by":"publisher","DOI":"10.1006\/dbio.1994.1077"},{"key":"e_1_2_12_45_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M608236200"},{"key":"e_1_2_12_46_1","doi-asserted-by":"publisher","DOI":"10.1083\/jcb.130.1.169"},{"key":"e_1_2_12_47_1","doi-asserted-by":"publisher","DOI":"10.1016\/0891-5849(96)02050-3"},{"key":"e_1_2_12_48_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0235361100"},{"issue":"1","key":"e_1_2_12_49_1","first-page":"231","article-title":"Transcription\u2010coupled Nucleotide Excision Repair Is Coordinated by Ubiquitin and SUMO in Response to Ultraviolet Irradiation","volume":"48","author":"Liebelt F.","year":"2020","journal-title":"Nucleic Acids Research"},{"key":"e_1_2_12_50_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1417548111"},{"key":"e_1_2_12_51_1","first-page":"204","article-title":"Repair in the rat lens after threshold ultraviolet radiation injury","volume":"41","author":"Michael R.","year":"2000","journal-title":"Investigative Ophthalmology & Visual Science"},{"key":"e_1_2_12_52_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.274.21.15115"},{"key":"e_1_2_12_53_1","doi-asserted-by":"publisher","DOI":"10.1038\/nn.2618"},{"key":"e_1_2_12_54_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuron.2008.12.006"},{"key":"e_1_2_12_55_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.H118.006240"},{"key":"e_1_2_12_56_1","doi-asserted-by":"publisher","DOI":"10.1111\/acel.12450"},{"key":"e_1_2_12_57_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M116.716621"},{"key":"e_1_2_12_58_1","first-page":"3247","article-title":"Glutathione peroxidase\u20101 deficiency leads to increased nuclear light scattering, membrane damage, and cataract formation in gene\u2010knockout mice","volume":"42","author":"Reddy V. N.","year":"2001","journal-title":"Investigative Ophthalmology & Visual Science"},{"key":"e_1_2_12_59_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.92.10.4676"},{"key":"e_1_2_12_60_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M110.142810"},{"key":"e_1_2_12_61_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1704351114"},{"key":"e_1_2_12_62_1","doi-asserted-by":"publisher","DOI":"10.1242\/dev.032888"},{"key":"e_1_2_12_63_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41576-019-0099-1"},{"key":"e_1_2_12_64_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.1092194"},{"key":"e_1_2_12_65_1","doi-asserted-by":"publisher","DOI":"10.1128\/MCB.19.7.5170"},{"key":"e_1_2_12_66_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1474-9726.2012.00860.x"},{"key":"e_1_2_12_67_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.1172871"},{"key":"e_1_2_12_68_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbagen.2015.08.016"},{"key":"e_1_2_12_69_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.mrrev.2019.02.004"},{"key":"e_1_2_12_70_1","doi-asserted-by":"publisher","DOI":"10.1111\/acel.12548"},{"key":"e_1_2_12_71_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbapap.2019.06.009"},{"key":"e_1_2_12_72_1","doi-asserted-by":"publisher","DOI":"10.1111\/acel.12164"},{"key":"e_1_2_12_73_1","doi-asserted-by":"publisher","DOI":"10.1101\/gad.7.11.2120"},{"key":"e_1_2_12_74_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.270.5240.1326"},{"key":"e_1_2_12_75_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1007866107"},{"key":"e_1_2_12_76_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1432-0436.2006.00068.x"},{"key":"e_1_2_12_77_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M611476200"},{"key":"e_1_2_12_78_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41422-018-0023-9"}],"container-title":["Aging Cell"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/acel.13222","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1111\/acel.13222","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/acel.13222","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,9,4]],"date-time":"2023-09-04T23:34:00Z","timestamp":1693870440000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/acel.13222"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,8,22]]},"references-count":77,"journal-issue":{"issue":"10","published-print":{"date-parts":[[2020,10]]}},"alternative-id":["10.1111\/acel.13222"],"URL":"https:\/\/doi.org\/10.1111\/acel.13222","archive":["Portico"],"relation":{},"ISSN":["1474-9718","1474-9726"],"issn-type":[{"value":"1474-9718","type":"print"},{"value":"1474-9726","type":"electronic"}],"subject":[],"published":{"date-parts":[[2020,8,22]]},"assertion":[{"value":"2020-02-15","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2020-07-26","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2020-08-22","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e13222"}}