Ask about this productRelated genes to: Fzr1 Blocking Peptide
- Gene:
- FZR1 NIH gene
- Name:
- fizzy and cell division cycle 20 related 1
- Previous symbol:
- -
- Synonyms:
- HCDH1, CDH1, HCDH, FZR, FZR2, KIAA1242, CDC20C
- Chromosome:
- 19p13.3
- Locus Type:
- gene with protein product
- Date approved:
- 2004-03-31
- Date modifiied:
- 2017-01-20
Related products to: Fzr1 Blocking Peptide
Related articles to: Fzr1 Blocking Peptide
- Centrosome duplication must be tightly regulated to maintain genomic stability. In Caenorhabditis elegans, the APC/C and co-activator FZR-1 function as negative regulators of centrosome duplication by targeting specific substrates for proteolytic degradation. While C. elegans SAS-5 and ZYG-1 have been identified as substrates of APC/CFZR-1, the mechanism by which APC/CFZR-1-dependent degradation influences centrosome assembly remains unclear. Here, we identified SPD-2, the conserved homolog of human CEP192, as an APC/CFZR-1 substrate. We show that loss of APC/CFZR-1 increases both cellular and centrosomal SPD-2 levels, and that SPD-2 physically associates with FZR-1 in vivo. Functional analyses of canonical D-box motifs reveal that D-box1, D-box2, and D-box3 each contribute to SPD-2 degradation, each with different functional consequences. Mutation of D-box3 alone partially rescued zyg-1 mutant phenotypes by restoring centrosome duplication and embryonic viability through increased centrosomal SPD-2 and ZYG-1. In contrast, mutating D-box1 or D-box2 elevated cellular SPD-2 but did not rescue zyg-1, with the D-box1 mutation further reducing centrosomal SPD-2 and exacerbating duplication defects and lethality in zyg-1 mutants. Our results reveal a conserved mechanism for APC/CFZR-1-dependent degradation of SPD-2 and indicate that SPD-2 stability is regulated by multiple D-box motifs, each associated with distinct functions, linking protein stability with centrosomal localization to ensure proper centrosome assembly during C. elegans embryogenesis. - Source: PubMed
Yim Rachel NDiPanni Joseph RRivera Paollette ASong Mi Hye - Preeclampsia (PE), a life-threatening hypertensive disorder of pregnancy, remains poorly characterized at the post-transcriptional regulation level. While alternative splicing (AS) perturbations drive pathological processes in numerous diseases, their systematic investigation in PE pathogenesis is lacking. - Source: PubMed
Publication date: 2026/03/19
Wang YanHuaLi WenXiaLi ZhiHuiQiang KePingShen JiangYongHuang LiJuan - Activation of retinoic acid-inducible gene-I-like receptors (RLRs) is important for type I interferon (IFN-I) production and antiviral innate immunity initiation. However, the epigenetic mechanisms that regulate RLR signaling remain poorly understood and require further investigation. Here, we demonstrate that Fizzy-related protein 1 (FZR1), which is essential for mitotic exit and G1/S transition, potentiates antiviral innate immune responses against RNA viruses. Mechanistically, vesicular stomatitis virus infection increases N6-methyladenosine (mA) modification of FZR1 mRNA, which enhances FZR1 translation and elevates intracellular FZR1 protein levels. Upregulated FZR1 attenuates mitochondrial antiviral-signaling protein (MAVS) binding to 6-Phosphofructo-2-Kinase/Fructose-2, 6-Biphosphatase 3, a glycolytic rate-limiting enzyme, thereby promoting MAVS aggregation. Furthermore, FZR1 facilitates tumor necrosis factor receptor-associated factor 3/6 (TRAF3/6) autoubiquitination independently of the anaphase-promoting complex/cyclosome, subsequently activating interferon regulatory factor 3 and P65 of nuclear factor κB to drive the production of IFN-I and proinflammatory cytokines. Consequently, FZR1 deficiency impairs antiviral responses and increases viral titer in vitro and in vivo. Pharmacological inhibition of FZR1 significantly attenuates MAVS activation and TRAF3/6 ubiquitination, thereby abolishing FZR1-mediated antiviral immunity both in vitro and in vivo. Collectively, these findings reveal a molecular mechanism by which mA modification of FZR1 activates the MAVS-TRAF3/6 signaling axis to potentiate IFN-I-dependent antiviral innate immunity. - Source: PubMed
Publication date: 2026/03/10
Dou KaiwenHu YiyiLi MingyangXu JialeZhang WeihaoWang HuiCheng QiJiang ZihaoChen LiangjunLiu ShiChen KeLiu YuanyuanXiong HairongLuo FanHou WeiChen Shuliang - Colorectal cancer (CRC) remains a leading cause of cancer-related mortality worldwide, underscoring the need to clarify its molecular drivers. Here, we identify DSN1 as a key promoter of CRC invasion and metastasis. Analysis of clinical samples and public datasets revealed that DSN1 is significantly upregulated in CRC tissues and associated with poor overall survival. Functional assays demonstrated that DSN1 knockdown markedly suppressed CRC cell migration and invasion in vitro and reduced metastases in vivo. Mechanistically, DSN1 knockdown accelerated c-MYC protein degradation without affecting its mRNA levels. Cycloheximide chase and proteasome inhibition assays confirmed that DSN1 stabilizes c-MYC by preventing its ubiquitin-proteasome-mediated degradation. We further identified FZR1 as a c-MYC targeting E3 ligase and showed that DSN1 competes with c-MYC for FZR1 binding, thereby attenuating c-MYC ubiquitination. Rescue experiments confirmed that c-MYC overexpression reversed the anti-metastatic effects of DSN1 silencing. Collectively, our findings uncover a DSN1-FZR1-c-MYC regulatory axis that sustains c-MYC stability and drives CRC progression, highlighting DSN1 as a potential therapeutic target. - Source: PubMed
Publication date: 2026/02/17
Zhang ChenkaiYuan ZimingHu HanqingWang ChunlinWang JiaqiXiang JunZhang NanaLi WenyangYu SongtaoGaliullin DanilArtur IbatullinZhang HaoWang Guiyu - Centrosome duplication must be tightly regulated to maintain genomic stability. In , the APC/C and co-activator FZR-1 function as negative regulators of centrosome duplication by targeting specific substrates for proteolytic degradation. While SAS-5 and ZYG-1 have been identified as substrates of APC/C, the mechanism by which APC/C-dependent degradation influences centrosome assembly remains unclear. Here, we identified SPD-2, the conserved homolog of human CEP192, as a substrate of APC/C. We show that loss of APC/C increases both cellular and centrosomal SPD-2 levels, and that SPD-2 physically associates with FZR-1 . Functional analyses of canonical D-box motifs reveal that D-box1, D-box2, and D-box3 each contribute to SPD-2 degradation, each with different functional consequences. Mutation of D-box3 alone partially rescued mutant phenotypes by restoring centrosome duplication and embryonic viability through increased centrosomal SPD-2 and ZYG-1. In contrast, mutating D-box1 or D-box2 elevated cellular SPD-2 but did not rescue , with the D-box1 mutation further reducing centrosomal SPD-2 and exacerbating duplication defects and lethality in mutants. Our results reveal a conserved mechanism for APC/C-dependent degradation of SPD-2 and show that its degron motifs have dual functions in degradation and centrosomal localization, ensuring robust control of centrosome assembly during embryogenesis. - Source: PubMed
Publication date: 2025/11/13
Yim Rachel NDiPanni Joseph RRivera Paollette ASong Mi Hye