Gene Symbol: Fzr1
Description: fizzy and cell division cycle 20 related 1
Alias: AW108046, Cdh1, FZR, FZR2, Fyr, HCDH, HCDH1, fizzy-related protein homolog, cdh1/Hct1 homolog, cell division cycle 20 related 1, fizzy/cell division cycle 20 related 1
Species: mouse
Products:     Fzr1

Top Publications

  1. Inbal N, Listovsky T, Brandeis M. The mammalian Fizzy and Fizzy-related genes are regulated at the transcriptional and post-transcriptional levels. FEBS Lett. 1999;463:350-4 pubmed
    ..The multisubunit cyclosome is regulated by transient interactions with Fizzy (Fzy) and Fizzy-related (Fzr) genes. We report here that both Fzy and Fzr are transcribed in a cell cycle specific but distinct manner...
  2. Konishi Y, Stegmuller J, Matsuda T, Bonni S, Bonni A. Cdh1-APC controls axonal growth and patterning in the mammalian brain. Science. 2004;303:1026-30 pubmed
    ..We report that the inhibition of Cdh1-APC in primary neurons specifically enhanced axonal growth...
  3. Li M, Shin Y, Hou L, Huang X, Wei Z, Klann E, et al. The adaptor protein of the anaphase promoting complex Cdh1 is essential in maintaining replicative lifespan and in learning and memory. Nat Cell Biol. 2008;10:1083-9 pubmed publisher
    ..Cdc20 (fizzy (fzy)) or p55CDC, and Cdh1 (Hct1, srw1 or fizzy-related 1 (fzr1)) encode two adaptor proteins that bring substrates to the APC...
  4. Garcia Higuera I, Manchado E, Dubus P, Canamero M, Mendez J, Moreno S, et al. Genomic stability and tumour suppression by the APC/C cofactor Cdh1. Nat Cell Biol. 2008;10:802-11 pubmed publisher
    The anaphase promoting complex or cyclosome (APC/C) is a ubiquitin protein ligase that, together with Cdc20 or Cdh1, targets cell-cycle proteins for degradation. APC/C-Cdh1 specifically promotes protein degradation in late mitosis and G1...
  5. Holt J, Tran S, Stewart J, Minahan K, Garcia Higuera I, Moreno S, et al. The APC/C activator FZR1 coordinates the timing of meiotic resumption during prophase I arrest in mammalian oocytes. Development. 2011;138:905-13 pubmed publisher
    b>FZR1, an activator of the anaphase-promoting complex/cyclosome (APC/C), is recognized for its roles in the mitotic cell cycle...
  6. Shoji S, Yoshida N, Amanai M, Ohgishi M, Fukui T, Fujimoto S, et al. Mammalian Emi2 mediates cytostatic arrest and transduces the signal for meiotic exit via Cdc20. EMBO J. 2006;25:834-45 pubmed
    ..These studies show in intact oocytes that the interaction of Emi2 with Cdc20 links activating stimuli to meiotic resumption at fertilization and during parthenogenesis in mammals. ..
  7. Marangos P, Verschuren E, Chen R, Jackson P, Carroll J. Prophase I arrest and progression to metaphase I in mouse oocytes are controlled by Emi1-dependent regulation of APC(Cdh1). J Cell Biol. 2007;176:65-75 pubmed
    ..Finally, we show that Emi1-dependent effects on meiosis I require the presence of Cdh1. These observations reveal a novel mechanism for the control of entry into the first meiotic division: an Emi1-..
  8. Schindler K, Schultz R. CDC14B acts through FZR1 (CDH1) to prevent meiotic maturation of mouse oocytes. Biol Reprod. 2009;80:795-803 pubmed publisher
    ..Depletion of FZR1 (CDH1), a regulatory subunit of the anaphase-promoting complex/cyclosome that targets cyclin B1 (CCNB1) for ubiquitin-..
  9. Sigl R, Wandke C, Rauch V, Kirk J, Hunt T, Geley S. Loss of the mammalian APC/C activator FZR1 shortens G1 and lengthens S phase but has little effect on exit from mitosis. J Cell Sci. 2009;122:4208-17 pubmed publisher
    ..to target securin and cyclin B1 for proteasome-dependent degradation, but then depends on the CDC20-related protein FZR1 (also known as CDH1) to remain active until the onset of the next S phase...

More Information


  1. Cheng R, Liang X, Zhao Q, Lian Z, Tang L, Qiu C, et al. APCCdh1 controls cell cycle entry during liver regeneration. Exp Cell Res. 2017;354:78-84 pubmed publisher
    b>Cdh1 is one of the two adaptor proteins of anaphase-promoting complex/cyclosome (APC/C), an E3 ubiquitin ligase controlling mitosis and DNA replication. To date, the in vivo functions of Cdh1 have not been fully explored...
  2. Serra H, Chivite I, Angulo Urarte A, Soler A, Sutherland J, Arruabarrena Aristorena A, et al. PTEN mediates Notch-dependent stalk cell arrest in angiogenesis. Nat Commun. 2015;6:7935 pubmed publisher
    ..We show that both the catalytic and non-catalytic APC/C-Fzr1/Cdh1-mediated activities of PTEN are required for stalk cells' proliferative arrest...
  3. Li M, York J, Zhang P. Loss of Cdc20 causes a securin-dependent metaphase arrest in two-cell mouse embryos. Mol Cell Biol. 2007;27:3481-8 pubmed
    ..The APC/C recognizes its substrates through two adapter proteins, Cdc20 and Cdh1, which contain similar C-terminal domains composed of seven WD-40 repeats believed to be involved in interacting ..
  4. Wang C, Fisk B, Wadehra M, Su H, Braun J. Overexpression of murine fizzy-related (fzr) increases natural killer cell-mediated cell death and suppresses tumor growth. Blood. 2000;96:259-63 pubmed
    Fizzy-related (fzr) is a recently identified 7WD domain family member implicated in cell cycle regulation of Drosophila and yeast...
  5. Bobo Jiménez V, Delgado Esteban M, Angibaud J, Sánchez Morán I, de la Fuente A, Yajeya J, et al. APC/CCdh1-Rock2 pathway controls dendritic integrity and memory. Proc Natl Acad Sci U S A. 2017;114:4513-4518 pubmed publisher
    ..However, the underlying molecular mechanisms are unknown. Here, we show that postnatal deletion of Cdh1, a cofactor of the anaphase-promoting complex/cyclosome (APC/C) ubiquitin ligase in neurons [Cdh1 conditional ..
  6. Ishizawa J, Kuninaka S, Sugihara E, Naoe H, Kobayashi Y, Chiyoda T, et al. The cell cycle regulator Cdh1 controls the pool sizes of hematopoietic stem cells and mature lineage progenitors by protecting from genotoxic stress. Cancer Sci. 2011;102:967-74 pubmed publisher
    ..b>Cdh1, one of the co-activators that maintain anaphase-promoting complex/cyclosome activity, plays a crucial role in the ..
  7. Erkeland S, Aarts L, Irandoust M, Roovers O, Klomp A, Valkhof M, et al. Novel role of WD40 and SOCS box protein-2 in steady-state distribution of granulocyte colony-stimulating factor receptor and G-CSF-controlled proliferation and differentiation signaling. Oncogene. 2007;26:1985-94 pubmed
    ..We conclude that control of forward routing of G-CSF-R is essential for a balanced response of myeloid progenitors to G-CSF and suggest that disturbance of this balance may contribute to myeloid leukemia. ..
  8. Wu G, Glickstein S, Liu W, Fujita T, Li W, Yang Q, et al. The anaphase-promoting complex coordinates initiation of lens differentiation. Mol Biol Cell. 2007;18:1018-29 pubmed
    ..We have identified that Cdh1/APC, a critical ubiquitin protein ligase, plays an important role in regulating lens differentiation by ..
  9. Song M, Carracedo A, Salmena L, Song S, Egia A, Malumbres M, et al. Nuclear PTEN regulates the APC-CDH1 tumor-suppressive complex in a phosphatase-independent manner. Cell. 2011;144:187-99 pubmed publisher
    ..Here we show that nuclear PTEN interacts with APC/C, promotes APC/C association with CDH1, and thereby enhances the tumor-suppressive activity of the APC-CDH1 complex...
  10. Zur A, Brandeis M. Securin degradation is mediated by fzy and fzr, and is required for complete chromatid separation but not for cytokinesis. EMBO J. 2001;20:792-801 pubmed
    ..contrast to budding yeast pds1, securin degradation is catalyzed by both fzy (fizzy/cdc20) and fzr (fizzy-related/cdh1/hct1). Both fzy and fzr also induce the APC/C to ubiquitinate securin in vitro...
  11. Wan L, Chen M, Cao J, Dai X, Yin Q, Zhang J, et al. The APC/C E3 Ligase Complex Activator FZR1 Restricts BRAF Oncogenic Function. Cancer Discov. 2017;7:424-441 pubmed publisher
    ..Here, we report that in primary cells with active APCFZR1, APCFZR1 earmarks BRAF for ubiquitination-mediated proteolysis, whereas in cancer cells with APC-..
  12. Chabes A, Pfleger C, Kirschner M, Thelander L. Mouse ribonucleotide reductase R2 protein: a new target for anaphase-promoting complex-Cdh1-mediated proteolysis. Proc Natl Acad Sci U S A. 2003;100:3925-9 pubmed
    ..degradation and hence the overall periodicity of R2 protein levels depends on a KEN box sequence, recognized by the Cdh1-anaphase-promoting complex...
  13. Holt J, Weaver J, Jones K. Spatial regulation of APCCdh1-induced cyclin B1 degradation maintains G2 arrest in mouse oocytes. Development. 2010;137:1297-304 pubmed publisher
    ..in the concentrations of the Cdk1-binding partner cyclin B1, a process achieved by anaphase-promoting complex (APC(Cdh1)) activity, which ubiquitylates and so targets cyclin B1 for degradation...
  14. Delgado Esteban M, Garcia Higuera I, Maestre C, Moreno S, Almeida A. APC/C-Cdh1 coordinates neurogenesis and cortical size during development. Nat Commun. 2013;4:2879 pubmed publisher
    ..Here we assessed whether the anaphase-promoting complex/cyclosome (APC/C) cofactor, Cdh1--which regulates mitosis exit and G1-phase length in dividing cells--regulates neurogenesis in vivo...
  15. Naoe H, Araki K, Nagano O, Kobayashi Y, Ishizawa J, Chiyoda T, et al. The anaphase-promoting complex/cyclosome activator Cdh1 modulates Rho GTPase by targeting p190 RhoGAP for degradation. Mol Cell Biol. 2010;30:3994-4005 pubmed publisher
    b>Cdh1 is an activator of the anaphase-promoting complex/cyclosome and contributes to mitotic exit and G(1) maintenance by targeting cell cycle proteins for degradation...
  16. Shenoy T, Boysen G, Wang M, Xu Q, Guo W, Koh F, et al. CHD1 loss sensitizes prostate cancer to DNA damaging therapy by promoting error-prone double-strand break repair. Ann Oncol. 2017;28:1495-1507 pubmed publisher
    ..We uncover mechanistic insights that CHD1 modulates the choice between HR and NHEJ DSB repair and suggest that CHD1 loss may contribute to the genomic instability seen in this subset of PCas. ..
  17. Pasque V, Radzisheuskaya A, Gillich A, Halley Stott R, Panamarova M, Zernicka Goetz M, et al. Histone variant macroH2A marks embryonic differentiation in vivo and acts as an epigenetic barrier to induced pluripotency. J Cell Sci. 2012;125:6094-104 pubmed publisher
  18. Seah M, Holt J, Garcia Higuera I, Moreno S, Jones K. The APC activator fizzy-related-1 (FZR1) is needed for preimplantation mouse embryo development. J Cell Sci. 2012;125:6030-7 pubmed publisher
    ..In contrast, fizzy-related-1 (FZR1), a non-essential protein in many cell types, is thought to play a role in APC activation at later cell cycles, and ..
  19. Huang J, Ikeuchi Y, Malumbres M, Bonni A. A Cdh1-APC/FMRP Ubiquitin Signaling Link Drives mGluR-Dependent Synaptic Plasticity in the Mammalian Brain. Neuron. 2015;86:726-39 pubmed publisher
    ..We report that conditional knockout of Cdh1, the key regulatory subunit of the ubiquitin ligase Cdh1-anaphase-promoting complex (Cdh1-APC), profoundly impairs ..
  20. Badodi S, Baruffaldi F, Ganassi M, Battini R, Molinari S. Phosphorylation-dependent degradation of MEF2C contributes to regulate G2/M transition. Cell Cycle. 2015;14:1517-28 pubmed publisher
    ..Our findings show that beside the well-established role as pro-myogenic transcription factor, MEF2C can also function as a regulator of cell proliferation. ..
  21. Holt J, Pye V, Boon E, Stewart J, Garcia Higuera I, Moreno S, et al. The APC/C activator FZR1 is essential for meiotic prophase I in mice. Development. 2014;141:1354-65 pubmed publisher
    Fizzy-related 1 (FZR1) is an activator of the Anaphase promoting complex/cyclosome (APC/C) and an important regulator of the mitotic cell division cycle...
  22. Kannan M, Lee S, Schwedhelm Domeyer N, Stegmuller J. The E3 ligase Cdh1-anaphase promoting complex operates upstream of the E3 ligase Smurf1 in the control of axon growth. Development. 2012;139:3600-12 pubmed publisher
    ..The E3 ubiquitin ligase Cdh1-anaphase promoting complex (APC) has emerged as an important intrinsic suppressor of axon growth...
  23. Eguren M, Porlan E, Manchado E, Garcia Higuera I, Canamero M, Farinas I, et al. The APC/C cofactor Cdh1 prevents replicative stress and p53-dependent cell death in neural progenitors. Nat Commun. 2013;4:2880 pubmed publisher
    The E3-ubiquitin ligase APC/C-Cdh1 is essential for endoreduplication but its relevance in the mammalian mitotic cell cycle is still unclear...
  24. Lane S, Jones K. Non-canonical function of spindle assembly checkpoint proteins after APC activation reduces aneuploidy in mouse oocytes. Nat Commun. 2014;5:3444 pubmed publisher
  25. Naoe H, Chiyoda T, Ishizawa J, Masuda K, Saya H, Kuninaka S. The APC/C activator Cdh1 regulates the G2/M transition during differentiation of placental trophoblast stem cells. Biochem Biophys Res Commun. 2013;430:757-62 pubmed publisher
    ..Here, we report that Cdh1, a regulator of the anaphase-promoting complex/cyclosome (APC/C), negatively regulates mitotic entry upon the ..
  26. Penas C, Govek E, Fang Y, Ramachandran V, Daniel M, Wang W, et al. Casein kinase 1δ is an APC/C(Cdh1) substrate that regulates cerebellar granule cell neurogenesis. Cell Rep. 2015;11:249-60 pubmed publisher
    ..CK1δ is targeted for proteolysis via the anaphase-promoting complex/cyclosome (APC/C(Cdh1)) ubiquitin ligase, and conditional deletion of the APC/C(Cdh1) activator Cdh1 in cerebellar GCPs results in higher ..
  27. Zhang J, Li H, Zhou T, Zhou J, Herrup K. Cdk5 levels oscillate during the neuronal cell cycle: Cdh1 ubiquitination triggers proteosome-dependent degradation during S-phase. J Biol Chem. 2012;287:25985-94 pubmed publisher
    ..a neuronal cell enters S phase, Cdk5 is transported to the cytoplasm where it is ubiquitinated by the E3 ligase APC-Cdh1. Ubiquitinated Cdk5 is then rapidly degraded by the proteasome...
  28. Holt J, Lane S, Jennings P, Garcia Higuera I, Moreno S, Jones K. APC(FZR1) prevents nondisjunction in mouse oocytes by controlling meiotic spindle assembly timing. Mol Biol Cell. 2012;23:3970-81 pubmed publisher
    b>FZR1 is an anaphase-promoting complex (APC) activator best known for its role in the mitotic cell cycle at M-phase exit, in G1, and in maintaining genome integrity...
  29. Ishizawa J, Sugihara E, Kuninaka S, Mogushi K, Kojima K, Benton C, et al. FZR1 loss increases sensitivity to DNA damage and consequently promotes murine and human B-cell acute leukemia. Blood. 2017;129:1958-1968 pubmed publisher
    FZR1 (fizzy-related protein homolog; also known as CDH1 [cell division cycle 20 related 1]) functions in the cell cycle as a specific activator of anaphase-promoting complex or cyclosome ubiquitin ligase, regulating late mitosis, G1
  30. Kim H, Vassilopoulos A, Wang R, Lahusen T, Xiao Z, Xu X, et al. SIRT2 maintains genome integrity and suppresses tumorigenesis through regulating APC/C activity. Cancer Cell. 2011;20:487-99 pubmed publisher
    ..SIRT2 regulates the anaphase-promoting complex/cyclosome activity through deacetylation of its coactivators, APC(CDH1) and CDC20...
  31. Zhou Y, Ching Y, Ng R, Jin D. Differential expression, localization and activity of two alternatively spliced isoforms of human APC regulator CDH1. Biochem J. 2003;374:349-58 pubmed
    ..to reveal the complex control of the APC through a regulatory network involving WD40 repeat proteins CDC20 and CDH1. In the present paper, we report on the identification and characterization of human CDH1beta, a novel ..