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Last update 08 May 2025

SAE1

Last update 08 May 2025

Basic Info

Synonyms

AOS1, FLJ3091, SAE1

+ [6]

Introduction

The heterodimer acts as an E1 ligase for SUMO1, SUMO2, SUMO3, and probably SUMO4. It mediates ATP-dependent activation of SUMO proteins followed by formation of a thioester bond between a SUMO protein and a conserved active site cysteine residue on UBA2/SAE2.

Drugs associated with SAE1

SB-4826

Target

SAE1

Mechanism

SAE1 inhibitors

Active Org.

Oncovalent Therapeutics, Inc.

Originator Org.

Oncovalent Therapeutics, Inc.

Active Indication

Neoplasms

Inactive Indication-

Drug Highest PhasePreclinical

First Approval Ctry. / Loc.-

First Approval Date20 Jan 1800

100 Clinical Results associated with SAE1

100 Translational Medicine associated with SAE1

0 Patents (Medical) associated with SAE1

218

Literatures (Medical) associated with SAE1

01 Jul 2025·Biochemical Pharmacology

Increased SUMO-activating enzyme subunit 1 promotes glycolysis and fibrotic phenotype of diabetic nephropathy

Article

Author: Sailike, Ali ; Haimiti, Shayila ; Wang, Yitian ; Wusiman, Reziwanguli ; Yang, Miaoyan ; Abuduaini, Hanikezi ; Gu, Meijun ; Gao, Lei

Renal fibrosis is a prominent feature of diabetic nephropathy (DN), and the connection between renal fibrosis and abnormal glycolysis is not fully understood. SUMO-activating enzyme subunit 1 (SAE1) plays a crucial role in the SUMO modification process and is related to abnormal glycolysis. Despite this, the specific role of SAE1 in DN and its mechanism are not well defined. To investigate this, a streptozotocin-induced diabetic CD1 mice model was used, with SAE1 suppression achieved through systemic administration of SAE1 siRNA. In parallel, human renal proximal tubular tubule HK2 cells transfected with siSAE1 were exposed to high glucose for in vitro studies. The study revealed that SAE1 levels were elevated in diabetic kidney, and the deletion of SAE1 mitigated renal fibrosis in DN mice. Such suppression in SAE1 was associated with the lower expression of hypoxia inducible factor-1α (HIF-1α) and 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase 3 (PFKFB3), these alterations subsequently improved abnormal glycolysis and mesenchymal transformations in vivo and in vitro. Further experiments discovered that SAE1 stabilized transcription factor HIF-1α expression through SUMOylation, promoting PFKFB3 transcription, which enhanced glycolysis characterized by increased PFK1 activity and lactate production. Additionally, pharmacological inhibition of PFKFB3 reduced renal fibrosis in DN mice, while overexpression of PFKFB3 partly restored the glycolysis and mesenchymal transformations inhibited by SAE1 knockdown in vitro. These data demonstrate that SAE1 promotes abnormal glycolysis by HIF-1α/PFKFB3 which is responsible for the fibrotic phenotype of diabetic kidney. Inhibition of SAE1 could be an alternative strategy in combating diabetes associated-kidney fibrosis via improving aberrant glycolysis.

01 Apr 2025·Plant, Cell & Environment

Plasticity of Root System Architecture and Whole Transcriptome Responses Underlying Nitrogen Deficiency Tolerance Conferred by a Wild Emmer Wheat QTL

Article

Author: Krugman, Tamar ; Govta, Nikolai ; Fahima, Tzion ; Beckles, Diane M. ; Peleg, Gadi ; Govta, Liubov ; Distelfeld, Assaf ; Sela, Hanan

ABSTRACTOur aim was to elucidate mechanisms underlying nitrogen (N)‐deficiency tolerance in bread wheat (cultivar Ruta), conferred by a wild emmer wheat QTL (WEW; IL99). We hypothesised that the tolerance in IL99 is driven by enhanced N‐uptake through modification of root system architecture (RSA) underscored by transcriptome modifications. Severe N‐deficiency (0.1 N for 26 days) triggered significantly higher plasticity in IL99 compared to Ruta by modifying 16 RSA traits; nine of which were IL99‐specific. The change in root growth in IL99 was collectively characterised by a transition in root orientation from shallow to steep, increased root number and length, and denser networks, enabling nutrient acquisition from a larger volume and deeper soil layers. Gene ontology and KEGG‐enrichment analyses highlighted IL99‐specific pathways and candidate genes elevated under N‐deficiency. This included Jasmonic acid metabolism, a key hormone mediating RSA plasticity (AOS1, TIFY, MTB2, MYC2), and lignification‐mediated root strengthening (CYP73A, 4CL). ‘N‐metabolism’ was identified as a main shared pathway to IL99 and Ruta, with enhanced nitrate uptake predominant in IL99 (NRT2.4), while remobilisation was the main strategy in Ruta (NRT2.3). These findings provide novel insights into wheat plasticity response underlying tolerance to N‐deficiency and demonstrate the potential of WEW for improving N‐uptake under suboptimal conditions.

01 Apr 2025·Rheumatology

Validation of the International Myositis Assessment and Clinical Studies Group guideline on cancer risk stratification

Article

Author: Li, Philip Hei ; Luk, Lucas Tsz Ho ; Chan, Shirley Chiu Wai ; Tang, Vivian Hoi Shan ; Lee, Patrick Man Leung ; Li, Wai Ling ; Ho, Roy ; So, Ho ; Chan, Dennis ; Lai, Billy Tin Lok ; Tang, Iris Yan Ki

AbstractObjectivesAdult-onset idiopathic inflammatory myopathies (IIMs) are associated with cancer. Guideline on cancer risk stratifications and screening in IIM patients was recently published, but their external validity remains verified. We evaluated its applicability and reliability among a Hong Kong IIM cohort.MethodsThe longitudinal observational cohort collected data from IIM patients fulfilling relevant classification criteria from eight rheumatology centres in Hong Kong. Demographic, clinical and laboratory data were reviewed from 2004 to 2023. IIM patients were stratified into standard, intermediate or high-risk subgroups according to the IMACS guideline. The occurrence of malignancy at or after IIM diagnosis was analysed. Independent risk factors for cancer were evaluated.ResultsA total of 479 patients were included with 327 females (68.3%) and mean age of IIM diagnosis at 54.5 ± 13.6 years. In total, 214 (44.7%) and 238 (49.7%) patients were stratified to high and intermediate risk groups, respectively. Only 5.6% belonged to the standard-risk group. Sixty patients (12.5%) had cancer within 3 years of IIM diagnosis. Nasopharyngeal (25%), lung (21.1%) and breast (10.5%) were the top three cancers. Significantly more patients (44, 20.6%) in the high-risk group developed cancer within 3 years, compared with intermediate (6.7%, P < 0.001) and standard-risk (0%, P = 0.009) groups. Risk factors for cancer included older age (OR: 1.048, 95%CI: 1.019–1.078), Gottron’s rash (OR: 2.453, 95%CI: 1.123–5.356), absence of interstitial lung disease (OR 2.695, 95% CI: 1.154–6.295), anti-TIF1g positivity (OR: 4.627, 95% CI: 2.046–10.461) and anti-SAE1 positivity (OR: 5.325, 95% CI: 1.271–22.300).ConclusionsOur real-world study supported the accuracy of cancer risk stratification. The vast majority of IIM patients would be subjected to extensive cancer screening when the guideline was applied.

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