Product Pathways - Cell Cycle / Checkpoint
APC6 (D8D8) Rabbit mAb #9499
|W IP||H M R Mk (B) (Dg) (Pg)||Endogenous||72||Rabbit IgG|
Reactivity Key: H=Human M=Mouse R=Rat Mk=Monkey B=Bovine Dg=Dog Pg=Pig
Species cross-reactivity is determined by western blot. Species enclosed in parentheses are predicted to react based on 100% sequence homology.
Specificity / Sensitivity
APC6 (D8D8) Rabbit mAb recognizes endogenous levels of total APC6 protein. Based upon sequence alignment, this antibody is not predicted to cross-react with either APC8/CDC23 or APC3/CDC27.
Source / Purification
Monoclonal antibody is produced by immunizing animals with a synthetic peptide corresponding to residues near the carboxy terminus of human APC6 protein.
Western blot analysis of extracts from 293T cells, either mock transfected (-) or transfected with a Myc/DDK-tagged cDNA expression construct encoding full-length human APC6 (hAPC6-Myc/DDK, +), using APC6 (D8D8) Rabbit mAb.
Cell proliferation in all eukaryotic cells depends strictly upon the ubiquitin ligase (E3) activity of the anaphase promoting complex/cyclosome (APC/C), whose main function is to trigger the transition of the cell cycle from metaphase to anaphase. APC/C is a 1.5 MDa protein complex found in the nucleus of interphase cells. This complex diffuses throughout the cytoplasm and associates with parts of the spindle apparatus during mitosis. APC/C performs its various functions by promoting the assembly of polyubiquitin chains on substrate proteins, which targets these proteins for degradation by the 26S proteasome (1,2). In humans, twelve different APC/C subunits have been identified. Like all E3 enzymes, APC/C utilizes ubiquitin residues that have been activated by E1 enzymes and then transferred to E2 enzymes. Indeed APC/C has been shown to transiently interact with UBCH5 and UBCH10 E2 enzymes, in part, via the RING-finger domain-containing subunit, APC11 (3-5). In addition to E2 enzymes, APC/C activity is also strictly dependent upon one of several cofactors that associate with APC/C during specific phases of the cell cycle. The best studied of these are Cdc20 and Cdh1, which contain a C-terminal WD40 domain and participate in the recognition of APC/C substrates by interacting with specific recognition elements in these substrates (6), called D-Boxes (7) and KEN-boxes (8).
APC6/CDC16 is a component of the tetratricopeptide repeat (TPR) sub-complex of the APC/C, which also consists of APC8/CDC23 and APC3/CDC27. It is thought that this sub-complex plays an important role in coordinating the juxtaposition of the catalytic and substrate recognition modules relative to co-activator, regulatory proteins, and substrates (9). There is also evidence suggesting that phosphorylation of APC6 and the other TPR subunits during mitosis plays a functional role in regulating the association between TPR subunits and substrate recognition subunits such as Cdc20 (10).
- Qiao, X. et al. (2010) Cell Cycle 9, 3904-12.
- Harper, J.W. et al. (2002) Genes Dev 16, 2179-206.
- Carroll, C.W. and Morgan, D.O. (2002) Nat Cell Biol 4, 880-7.
- Gmachl, M. et al. (2000) Proc Natl Acad Sci U S A 97, 8973-8.
- Leverson, J.D. et al. (2000) Mol Biol Cell 11, 2315-25.
- Kraft, C. et al. (2005) Mol Cell 18, 543-53.
- Glotzer, M. et al. (1991) Nature 349, 132-8.
- Pfleger, C.M. and Kirschner, M.W. (2000) Genes Dev 14, 655-65.
- Schreiber, A. et al. (2011) Nature 470, 227-32.
- Kraft, C. et al. (2003) EMBO J 22, 6598-609.
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