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Rabbit Anti-FZR1/FITC Conjugated antibody
background:
Fizzy-related protein, known as fzr, is a conserved eukaryotic gene that has been recently identified as a 7WD domain family member and is implicated in cell cycle regulation of Drosophila and yeast. Retroviral overexpression of fzr in B-lymphoma cells reduces tumor formation. Fzr overexpression increases B-lymphoma cell susceptibility to natural killer cell (NK) cytotoxicity. Fzr has been implicated in a new category of genes which suppress B-cell tumorigenesis. Current research suggests a novel role for fzr in the target cell interaction with NK cells. Fzr also negatively regulates the levels of cyclins A, B and B3. Loss of fzr causes progression through an extra division cycle in the epidermis and inhibition of endoreduplication in the salivary gland, in addition to failure of cyclin removal. Conversely, premature fzr overexpression downregulates mitotic cyclins, inhibits mitosis and transforms mitotic cycles into endoreduplication cycles.
Function:
Key regulator of ligase activity of the anaphase promoting complex/cyclosome (APC/C), which confers substrate specificity upon the complex. Associates with the APC/C in late mitosis, in replacement of CDC20, and activates the APC/C during anaphase and telophase. The APC/C remains active in degrading substrates to ensure that positive regulators of the cell cycle do not accumulate prematurely. At the G1/S transition FZR1 is phosphorylated, leading to its dissociation from the APC/C. Following DNA damage, it is required for the G2 DNA damage checkpoint: its dephosphorylation and reassociation with the APC/C leads to the ubiquitination of PLK1, preventing entry into mitosis.
Subunit:
The unphosphorylated form interacts with APC/C during mitosis. Interacts with NINL. Interacts (in complex with the anaphase promoting complex APC) with MAD2L2; inhibits FZR1-mediated APC/C activation. Interacts with USP37. Interacts (via WD repeats) with MAK.
Subcellular Location:
Cytoplasm and Nucleus.
Tissue Specificity:
Isoform 2 is expressed at high levels in heart, liver, spleen and some cancer cell lines whereas isoform 3 is expressed only at low levels in these tissues.
Post-translational modifications:
Phosphorylated during mitosis, probably by maturation promoting factor (MPF), leading to its dissociation of the APC/C. Following DNA damage, it is dephosphorylated by CDC14B in G2 phase, leading to its reassociation with the APC/C, and allowing an efficient G2 DNA damage checkpoint.
Similarity:
Belongs to the WD repeat CDC20/Fizzy family.
Contains 7 WD repeats.
Database links:
Entrez Gene: 51343 Human
Entrez Gene: 56371 Mouse
Omim: 603619 Human
SwissProt: Q9UM11 Human
SwissProt: Q9R1K5 Mouse
Unigene: 413133 Human
Unigene: 24202 Mouse
Important Note:
This product as supplied is intended for research use only, not for use in human, therapeutic or diagnostic applications.
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