Ask about this productRelated genes to: PPPDE1 antibody
- Gene:
- DESI2 NIH gene
- Name:
- desumoylating isopeptidase 2
- Previous symbol:
- C1orf121, FAM152A, PPPDE1
- Synonyms:
- CGI-146, FLJ21998, PNAS-4
- Chromosome:
- 1q44
- Locus Type:
- gene with protein product
- Date approved:
- 2005-06-21
- Date modifiied:
- 2015-06-12
Related products to: PPPDE1 antibody
Related articles to: PPPDE1 antibody
- The JAK2-V617F mutation is the most common genetic alteration in myeloproliferative neoplasms (MPN), which can progress to secondary acute myeloid leukemia (sAML), a chemotherapy-resistant disease with limited treatment options and a poor prognosis. Although the JAK1/2 inhibitor Ruxolitinib is clinically approved, its efficacy is limited by toxicity to normal cells and the development of drug resistance. Here, the deSUMOylase DESI2 is identified as a novel component of the JAK2-V617F complex by mass spectrometry-based proteomics. Mechanistically, DESI2 selectively binds to and stabilizes JAK2-V617F by mediating its deSUMOylation and deubiquitination at lysine 962 (K962). Importantly, DESI2 protein is specifically and highly expressed in JAK2-mutant-driven cell lines and MPN primary clinical samples, suggesting its potential role in JAK2-V617F regulation and disease progression. Genetic depletion of DESI2 suppresses both JAK2 mutant cell growth and MPN disease onset in vitro and in vivo. Moreover, through a compound screen, followed by chemical proteomics and compound optimization, WWQ-03-012 is discovered, which selectively degrades mutant JAK2, induces primary leukemia cells death, and inhibits MPN progression through targeting DESI2 enzymatic activity in vitro and in vivo. These studies provide a novel therapeutic strategy against mutated JAK2 signaling in MPN and sAML. - Source: PubMed
Publication date: 2025/12/03
Mei HushengWen WuqiangZhang WenjunZhang ShujingSun TingLi GuimingZhang JingQi ShuangZhou JieLi BingZhao YunshuoChen XiaotongLi BowenXue YiyingLu WangSun YanliWang JingyaoShan HengyueZhang ShengzheHuang YushanChen YisaWang WenchaoLiu QingsongLu WenchaoTan LiDing YiFu JianfeiLong JunZhang LeiZhao BaobingLiang AibinJiang BaishanYang Jing - Ubiquitin-specific protease 30 (USP30) is a deubiquitinating enzyme (DUB) localized at the mitochondrial outer membrane and involved in PINK1/Parkin-mediated mitophagy, pexophagy, BAX/BAK-dependent apoptosis, and IKKβ-USP30-ACLY-regulated lipogenesis/tumorigenesis. A USP30 inhibitor, MTX652, has recently entered clinical trials as a potential treatment for mitochondrial dysfunction. Small molecule activity-based probes (ABPs) for DUBs have recently emerged as powerful tools for in-cell inhibitor screening and DUB activity analysis, and here, we report the first small molecule ABPs (IMP-2587 and IMP-2586) which can profile USP30 activity in cells. Target engagement studies demonstrate that IMP-2587 and IMP-2586 engage active USP30 at nanomolar concentration after only 10 min incubation time in intact cells, dependent on the presence of the USP30 catalytic cysteine. Interestingly, proteomics analyses revealed that DESI1 and DESI2, small ubiquitin-related modifier (SUMO) proteases, can also be engaged by these probes, further suggesting a novel approach to develop DESI ABPs. - Source: PubMed
Publication date: 2024/03/13
Mondal MilonCao FangyuanConole DanielAuner Holger WTate Edward W - The potato's most devastating disease is late blight, which is caused by Phytophthora infestans. Whereas various resistance (R) genes are known, most are typically defeated by this fast-evolving oomycete pathogen. However, the broad-spectrum and durable R8 is a vital gene resource for potato resistance breeding. To support an educated deployment of R8, we embarked on a study on the corresponding avirulence gene Avr8. We overexpressed Avr8 by transient and stable transformation, and found that Avr8 promotes colonization of P. infestans in Nicotiana benthamiana and potato, respectively. A yeast-two-hybrid (Y2H) screen showed that AVR8 interacts with a desumoylating isopeptidase (StDeSI2) of potato. We overexpressed DeSI2 and found that DeSI2 positively regulates resistance to P. infestans, while silencing StDeSI2 downregulated the expression of a set of defense-related genes. By using a specific proteasome inhibitor, we found that AVR8 destabilized StDeSI2 through the 26S proteasome and attenuated early PTI responses. Altogether, these results indicate that AVR8 manipulates desumoylation, which is a new strategy that adds to the plethora of mechanisms that Phytophthora exploits to modulate host immunity, and StDeSI2 provides a new target for durable resistance breeding against P. infestans in potato. - Source: PubMed
Publication date: 2023/05/10
Jiang RuiHe QinSong JingyiLiu ZengYu JianHu KefanLiu HuimingMu YangWu JiahuiTian ZhendongSong BotaoVleeshouwers Vivianne G A AXie ConghuaDu Juan - Chickpeas are a very important legume crop and have abundant protein, carbohydrate, lipid, fiber, isoflavone, and mineral contents. The chemical compositions of the four chickpea species (Muying-1, Keying-1, Desi-1, Desi-2) from Xinjiang, China, were analyzed, and 46 different flavonoids in Muying-1 were detected. The moisture content ranged from 7.64 ± 0.01 to 7.89 ± 0.02 g/100 g, the content of starch in the kabuli chickpeas was greater than that in the desi chickpeas, the total ash content ranged from 2.59 ± 0.05 to 2.69 ± 0.03 g/100 g and the vitamin B content of the chickpeas ranged from 0.31 to 0.36 mg/100 g. The lipid content ranged from 6.35 to 9.35 g/100 g and the major fatty acids of chickpeas were linoleic, oleic, and palmitic acids. Both kabuli and desi chickpeas have a high content of unsaturated fatty acids (USFAs), Muying-1 and Desi-1 contained the highest level of linoleic acid, and Keying-1 had the highest oleic acid content. The protein level ranged from 19.79 ± 2.89 to 23.38 ± 0.30 g/100 g, and the main amino acids were aspartic acid, glutamic acid, and arginine acid. The four chickpea species had significant amounts of essential amino acids (EAAs). Forty-six varieties of flavonoids in Muying-1 were determined by ultra high-performance liquid chromatography coupled with triple quadrupole mass spectrometry (UPLC-QqQ-MS) analysis, and there were higher levels of conjugate flavonoids (55.95%) than free flavonoids (44.05%). Isoflavones were the most abundant flavonoids in Muying-1, and among the isoflavones, daidzin had the highest content, followed by biochanin A and genistin. Muying-1 was rich in daidzin, biochanin A, genistin, troxerutin, isorhamnetin, astilbin, L-epicatechin, astragalin, acacetin, hyperoside, and myricitrin. Information provided in the study will be helpful to further understand the chemical composition of chickpeas and be beneficial to the development of chickpeas. - Source: PubMed
Publication date: 2022/09/15
Xiao ShiqiLi ZhengleiZhou KeqiangFu Yinghua - Congenital anorectal malformations (ARMs) are among the most prominent deformities of the gastrointestinal tract; however, their precise aetiology remains obscure. Immunohistochemistry demonstrated that, in the ARM group, the PPPDE1-positive cells were widely distributed in the hindgut epithelial tissue from GD13 to GD16. Immunofluorescence revealed that most TUNEL-, Bax-, and Cytochrome C (Cyt C)-positive cells overlapped with PPPDE1-positive cells in the urorectal septum (URS). Western blotting and quantitative real-time RT-PCR revealed that PPPDE1 levels were significantly higher in the ARM group from GD13 to GD14 (p < 0.05). IEC-6 cells were transfected with PPPDE1 overexpression plasmid/NC (negative control) or si-PPPDE1/si-NC. Flow cytometry analysis and CCK-8 assay (used to detect apoptosis and proliferation, respectively), as well as western blotting, showed that the levels of PPPDE1 were positively correlated with the pro-apoptotic molecules Bax and Cyt C. Accordingly, aberrantly high expression of PPPDE1 caused a spatiotemporal imbalance in foetal rats with ARMs during hindgut development. Therefore, the upregulation of PPPDE1 may promote epithelial apoptosis and reduce proliferation in the hindgut via the mitochondrial apoptotic pathway. This could affect the fusion of the URS and cloacal membrane, ultimately inhibiting the hindgut development and resulting in ARMs. - Source: PubMed
Publication date: 2021/03/29
Li Si YingWang Chen YiZhao Jing JingLong Cai YunXiao Yun XiaTang Xiao BingYuan Zheng WeiBai Yu Zuo