File Download
  Links for fulltext
     (May Require Subscription)
Supplementary

Article: SENP1-mediated deSUMOylation of JAK2 regulates its kinase activity and platinum drug resistance

TitleSENP1-mediated deSUMOylation of JAK2 regulates its kinase activity and platinum drug resistance
Authors
Issue Date2021
PublisherNature Publishing Group: Open Access Journals. The Journal's web site is located at http://www.nature.com/cddis/index.html
Citation
Cell Death & Disease, 2021, v. 12, p. article no. 341 How to Cite?
AbstractThe JAK2/STAT pathway is hyperactivated in many cancers, and such hyperactivation is associated with a poor clinical prognosis and drug resistance. The mechanism regulating JAK2 activity is complex. Although translocation of JAK2 between nucleus and cytoplasm is an important regulatory mechanism, how JAK2 translocation is regulated and what is the physiological function of this translocation remain largely unknown. Here, we found that protease SENP1 directly interacts with and deSUMOylates JAK2, and the deSUMOylation of JAK2 leads to its accumulation at cytoplasm, where JAK2 is activated. Significantly, this novel SENP1/JAK2 axis is activated in platinum-resistant ovarian cancer in a manner dependent on a transcription factor RUNX2 and activated RUNX2/SENP1/JAK2 is critical for platinum-resistance in ovarian cancer. To explore the application of anti-SENP1/JAK2 for treatment of platinum-resistant ovarian cancer, we found SENP1 deficiency or treatment by SENP1 inhibitor Momordin Ic significantly overcomes platinum-resistance of ovarian cancer. Thus, this study not only identifies a novel mechanism regulating JAK2 activity, but also provides with a potential approach to treat platinum-resistant ovarian cancer by targeting SENP1/JAK2 pathway.
Persistent Identifierhttp://hdl.handle.net/10722/300709
ISSN
2023 Impact Factor: 8.1
2023 SCImago Journal Rankings: 2.447
PubMed Central ID
ISI Accession Number ID

 

DC FieldValueLanguage
dc.contributor.authorLi, J-
dc.contributor.authorWu, R-
dc.contributor.authorYung, MMH-
dc.contributor.authorSun, J-
dc.contributor.authorLi, Z-
dc.contributor.authorYang, H-
dc.contributor.authorZhang, Y-
dc.contributor.authorLiu, S-
dc.contributor.authorCheung, ANY-
dc.contributor.authorNgan, HYS-
dc.contributor.authorBraisted, JC-
dc.contributor.authorZheng, W-
dc.contributor.authorWei, H-
dc.contributor.authorGao, Y-
dc.contributor.authorNemes, P-
dc.contributor.authorPei, H-
dc.contributor.authorChan, DW-
dc.contributor.authorLi, Y-
dc.contributor.authorZhu, W-
dc.date.accessioned2021-06-18T14:55:56Z-
dc.date.available2021-06-18T14:55:56Z-
dc.date.issued2021-
dc.identifier.citationCell Death & Disease, 2021, v. 12, p. article no. 341-
dc.identifier.issn2041-4889-
dc.identifier.urihttp://hdl.handle.net/10722/300709-
dc.description.abstractThe JAK2/STAT pathway is hyperactivated in many cancers, and such hyperactivation is associated with a poor clinical prognosis and drug resistance. The mechanism regulating JAK2 activity is complex. Although translocation of JAK2 between nucleus and cytoplasm is an important regulatory mechanism, how JAK2 translocation is regulated and what is the physiological function of this translocation remain largely unknown. Here, we found that protease SENP1 directly interacts with and deSUMOylates JAK2, and the deSUMOylation of JAK2 leads to its accumulation at cytoplasm, where JAK2 is activated. Significantly, this novel SENP1/JAK2 axis is activated in platinum-resistant ovarian cancer in a manner dependent on a transcription factor RUNX2 and activated RUNX2/SENP1/JAK2 is critical for platinum-resistance in ovarian cancer. To explore the application of anti-SENP1/JAK2 for treatment of platinum-resistant ovarian cancer, we found SENP1 deficiency or treatment by SENP1 inhibitor Momordin Ic significantly overcomes platinum-resistance of ovarian cancer. Thus, this study not only identifies a novel mechanism regulating JAK2 activity, but also provides with a potential approach to treat platinum-resistant ovarian cancer by targeting SENP1/JAK2 pathway.-
dc.languageeng-
dc.publisherNature Publishing Group: Open Access Journals. The Journal's web site is located at http://www.nature.com/cddis/index.html-
dc.relation.ispartofCell Death & Disease-
dc.rightsThis work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License.-
dc.titleSENP1-mediated deSUMOylation of JAK2 regulates its kinase activity and platinum drug resistance-
dc.typeArticle-
dc.identifier.emailYung, MMH: mhyung@hku.hk-
dc.identifier.emailLiu, S: stephasl@hku.hk-
dc.identifier.emailCheung, ANY: anycheun@hkucc.hku.hk-
dc.identifier.emailNgan, HYS: hysngan@hkucc.hku.hk-
dc.identifier.emailChan, DW: dwchan@hku.hk-
dc.identifier.authorityLiu, S=rp00372-
dc.identifier.authorityCheung, ANY=rp00542-
dc.identifier.authorityNgan, HYS=rp00346-
dc.identifier.authorityChan, DW=rp00543-
dc.description.naturepublished_or_final_version-
dc.identifier.doi10.1038/s41419-021-03635-6-
dc.identifier.pmid33795649-
dc.identifier.pmcidPMC8016909-
dc.identifier.scopuseid_2-s2.0-85103671641-
dc.identifier.hkuros322766-
dc.identifier.volume12-
dc.identifier.spagearticle no. 341-
dc.identifier.epagearticle no. 341-
dc.identifier.isiWOS:000636735700006-
dc.publisher.placeUnited Kingdom-

Export via OAI-PMH Interface in XML Formats


OR


Export to Other Non-XML Formats