High impact information on fzy

• While Drosophila fizzy has previously been shown to be required for cyclin destruction during M phase, fzr is required for cyclin removal during G1 when the embryonic epidermal cell proliferation stops and during G2 preceding salivary gland endoreduplication [1].
• Moreover, cells arrested in mitosis before sister chromatid separation (by colcemid or by mutations in fizzy/CDC20) fail to degrade PIM [2].
• The roles of Fzy/Cdc20 and Fzr/Cdh1 in regulating the destruction of cyclin B in space and time [3].
• A destruction box-mutated form of cyclin B (cyclin B triple-point mutant [CBTPM]-GFP) that cannot be targeted for destruction by Fzy/Cdc20, is no longer degraded on spindles in syncytial embryos [3].
• We show that the APC/C regulators Fizzy (Fzy)/Cdc20 and Fzy-related (Fzr)/Cdh1 bind to microtubules in vitro and associate with spindles in vivo [3].

Biological context of fzy

• Fzy/Cdc20 is concentrated at kinetochores and centrosomes early in mitosis, whereas Fzr/Cdh1 is concentrated at centrosomes throughout the cell cycle [3].
• Mutations affecting chromatid separation in Drosophila: the fizzy metaphase arrest persists in pimples fizzy and fizzy three rows double mutants [4].
• The metaphase arrest phenotype caused by fzy mutations is associated with failure to degrade both mitotic cyclins A and B, and an enrichment of spindle microtubules at the expense of astral microtubules [5].
• During interphase fzy protein is present in the cytoplasm; while in mitosis fzy becomes ubiquitously distributed throughout the cell except for the area occupied by the chromosomes [5].
• In early embryos fzy is expressed in all proliferating tissues; in late embryos fzy expression declines in a tissue-specific manner correlated with cessation of cell division [5].

Anatomical context of fzy

• We show that maternally supplied fizzy activity is required for normal nuclear division in the preblastoderm embryo and, during later embryogenesis, that zygotic fizzy activity is required for the development of the ventrally derived epidermis and the central and peripheral nervous systems [6].

Other interactions of fzy

• APC activity is restricted to mitotic stages and G1 by its activators Cdc20-Fizzy (Cdc20(Fzy)) and Cdh1-Fizzy-related (Cdh1(Fzr)), respectively [7].
• Drosophila female meiosis and embryonic syncytial mitosis use specialized Cks and CDC20 proteins for cyclin destruction [8].
• We show that Cort functions together with the canonical mitotic APC adaptor Fzy to target the three mitotic cyclins (A, B and B3) for destruction in the egg and drive anaphase progression in both meiotic divisions [9].

Analytical, diagnostic and therapeutic context of fzy

• Sequence analysis predicts that fzy encodes a protein of 526 amino acids, the carboxy half of which has significant homology to the Saccharomyces cerevisiae cell cycle gene CDC20 [5].

References