Ask about this productRelated genes to: FBXO22 Blocking Peptide
- Gene:
- FBXO22 NIH gene
- Name:
- F-box protein 22
- Previous symbol:
- -
- Synonyms:
- FBX22, FISTC1
- Chromosome:
- 15q24.2
- Locus Type:
- gene with protein product
- Date approved:
- 2000-09-27
- Date modifiied:
- 2016-10-05
Related products to: FBXO22 Blocking Peptide
Related articles to: FBXO22 Blocking Peptide
- Targeted protein degradation (TPD) through the ubiquitin-proteasome system is driven by compound-mediated polyubiquitination of a protein-of-interest by an E3 ubiquitin (Ub) ligase. Relatively few E3s have been successfully utilized for TPD and the governing principles of functional ternary complex formation between the E3, degrader, and protein target remain elusive. FBXO22 has recently been harnessed for TPD applications by degraders that covalently modify its cysteine residues. Here, we reveal that the aldehyde derivative of UNC10088 promotes cooperative binding of FBXO22 to NSD2, a histone methyltransferase and oncogenic protein, leading to a cryo-EM structure of the SKP1-CUL1-F-box (SCF)-FBXO22 complex with NSD2. This structure revealed a conformational change in the FBXO22 loop surrounding C326, further exposing the cysteine for covalent recruitment. Additional medicinal chemistry efforts led to the discovery of benzaldehyde-based non-prodrug degraders that similarly engage C326 of FBXO22 and potently degrade NSD2. Unlike many degraders, our molecules recruit NSD2 to a different surface of FBXO22 than the known FBXO22 substrate BACH1, allowing for concurrent complex formation and structural determination of SCF bound to both the neosubstrate NSD2 and native substrate BACH1. Overall, we demonstrate the biochemical and structural basis for NSD2 degradation, revealing key principles for efficient and selective TPD by SCF. - Source: PubMed
Publication date: 2026/04/23
Robertson Kevin CAmann Sascha JLiu TongkunFunk Adam VWang XianxiGrishkovskaya IrinaMehmood AamirTabor John RNorris-Drouin Jacqueline LArrowsmith Cheryl HCollins Jon LMiao YinglongEmanuele Michael JHaselbach DavidJames Lindsey IBrown Nicholas G - Leukemia is a malignant clonal disease originating from hematopoietic stem cells. Uncontrolled proliferation, impaired differentiation and maturation, accompanied by reduced apoptosis is the most significant feature of leukemia. It has been suggested that c-Cbl is involved in the development of myeloid leukemia, but the upstream signal regulating its activity remains unclear. FBXO22 is an E3 ubiquitin ligase belonging to the F-box protein family. We constructed stable cell lines of the overexpression of FBXO22 and c-Cbl, the knockdout of c-Cbl as well as FBXO22 + c-Cbl co-transfection. We used CCK-8 and FACS to measure the cell viability, cell cycle and cell differentiation, respectively. After overexpression of FBXO22, the proliferation of U937 and K562 cells was slowed down, the pro-apoptotic proteins were increased, the anti-apoptotic proteins were decreased, and the cells differentiated into the next stage. The result of c-Cbl knockdown was consistent with that of FBXO22 overexpression. Overexpression of c-Cbl showed the opposite result. In vivo experiments also showed that both FBXO22 overexpression and c-Cbl knockdown could inhibit the occurrence and development of leukemia. Immunoprecipitation result showed that FBXO22 interacted with c-Cbl and promoted ubiquitination and degradation of c-Cbl. Moreover, the results of rescue experiments showed that c-Cbl reversed the function of FBXO22 on leukemia cells. We identified that FBXO22 interacts with c-Cbl and promotes its ubiquitination and degradation to act as a tumor suppressor gene in leukemia. Our studies suggested that FBXO22 plays an anticancer role by mediating ubiquitination and degradation of c-Cbl in leukemia. - Source: PubMed
Publication date: 2026/02/26
Li JuanMa LiWang JingXu WangwangCheng YangZhang JialinCao HairuoWang YuWang ZhiweiXu HuiLi YuyunZhang Yingjie - The body-protective polypeptide BPC157 is a natural therapeutic agent that has demonstrated robust efficacy in promoting repair across multiple organ systems, indicating its significant clinical potential. However, its clinical translation has been substantially hindered by a lack of understanding of its precise molecular mechanisms of action. Given its prominent proangiogenic effects, deciphering the mechanistic basis of its vascular regenerative actions is critically important. - Source: PubMed
Publication date: 2026/01/29
Zhang JieyuLiu MengmengOu HuihuiWang ZhaoweiHe LeiXiao YangXie FeiYu DuoCao HaiyanHe WeiWang ShuningZhang WangqianZhang KuoZhang YingqiLi MengHao Qiang - Nucleus pulposus (NP) cell ageing and impaired autophagy - lysosome biogenesis (ALB) are key drivers of intervertebral disc degeneration (IVDD). The upstream epigenetic regulation of transcription factor EB (TFEB), a major ALB regulator, remains elusive. Our study identifies a H3K4me3-associated miRNA pathway that modulates TFEB activity and IVDD progression. Using and models, we found that methyltransferase MLL3 knockdown reduces H3K4me3 methylation at the miR-155-5p promoter, suppressing miR-155-5p transcription. MiR-155-5p directly targets FBXO22, indirectly repressing TFEB transcription and exacerbating NP cells ageing and IVDD. Notably, experiments confirmed MLL3 binds specifically to the miR-155-5p promoter, with no interaction detected at the TFEB or FBXO22 promoters. Our data establish a linear H3K4me3/miR-155-5p/FBXO22/TFEB axis in IVDD pathogenesis. We reveal a novel epigenetic crosstalk where H3K4me3 methylation mediates miRNA-driven TFEB regulation, independent of canonical mTOR signaling. These findings enhance understanding of epigenetic mechanisms in autophagy and ageing control and highlight MLL3 and miR-155-5p as potential IVDD therapeutic targets. - Source: PubMed
Publication date: 2025/12/26
Wang XimengSun HanqiuXiao WenbiaoZhang YuxuanLu XiaoGong ZhaoyangLi DachuanLiu SiyangXia XinleiWang HongliShao MinghaoXu GuangyuMa Xiaosheng - Intervertebral disc degeneration (IVDD) is a predominant cause of low back pain, and mesenchymal stem cell (MSC) transplantation represents a promising therapeutic strategy. However, its efficacy is severely limited by the harsh oxidative microenvironment of the degenerative disc, which rapidly triggers ferroptosis, an iron-dependent form of cell death, in transplanted MSCs. - Source: PubMed
Publication date: 2026/01/13
Xu YuzhuQian ZhanyangJi MingliangLu Jun