Identification and functional characterisation of novel APC/C interacting proteins

摘要: The anaphase promoting complex /cyclosome (APC/C) is a multi-protein E3 ubiquitin ligase that regulates cellular proliferation through its ability to target essential cell cycle regulators such as cyclin A, B, securin and S-phase kinase-associated protein 2 (SKP2) for proteasomal-dependent degradation. APC/C substrates coactivators are aberrantly expressed in many cancers. It thought the can also regulate by controlling p21 division 6 homologue (CDC6) transcription. therefore of great interest study other proteins interact with these may be important regulation hence enhance our understanding molecular basis cancer. Therefore, aim my was identify novel interacting mass spectrometric analysis subunit 7 (APC7) immunoprecipitates go on examine functional significance interactions. I identified six APC7 proteins, decided focus two Initially examined interaction between transcriptional intermediary factor 1\(\gamma\) (TIF1\(\gamma\)), repressor previously reported Data presented this demonstrate TIF1\(\gamma\) cooperate mitotic progression. Notably displays vivo interactions subunits 1-8, APC/C‟s coactivator CDC20 substrate A. Moreover, depletion RNAi arrests cells metaphase-like state characterised elevated levels substrates, B CDC20. In support role regulating progression directly targeting APC/C, treated TIF1\(\gamma\)-specific siRNA exhibit reduced activity. This work defines regulatory function suggests loss compromise genomic integrity allowing mis-segregation chromosomes. investigated relationship nuclear 90/45 heterodimer (NF90/NF45), given all transcription factors. Results obtained APC5 bind NF90 vitro form complexes vivo. appears interleukin-2 (IL-2) tumour neucrosis (TNF) transcription, exogenous NF90/NF45 transactivate IL-2 TNF promoter constructs. Lastly endogenous while represses Given stimulate data here might control