Regulation of mitosis : molecular analysis of the anaphase-promoting complex

摘要: Regulation of mitosis molecular analysis the anaphase-promoting complex. Thesis by Pia-Marie Jorgensen, Department Cell and Molecular Biology, Division Genetics, Karolinska Institutet, S-171 77 Stockholm division is achieved progression through a series events known as cell cycle. To make sure that original copied with high fidelity, an elaborate control system using so called checkpoints employed, preventing cycle to occur prematurely or in wrong order. Chromosome segregation important process must be performed correctly ensure two resulting daughter cells have same DNA content. Missegregation chromosomes results aneuploidy, something frequently found cancers, suggesting machinery surveying chromosome has somehow been compromised during development these tumours. One checkpoints, mitotic spindle checkpoint, also shown defective cancers chromosomal instability. The which monitors metaphase anaphase transition, involves e.g. Mad Bub proteins makes each attached functional before giving signal separate sister chromatids. This relayed complex Anaphase Promoting Complex Cyclosome, APC/C. APC/C ubiquitin ligase, E3, targets regulatory for degradation proteasome, thereby allowing regulated phosphorylation proteins, Cdc20 Cdh1, affect activity early late mitosis/G1 respectively. interact assembly checkpoint protein Mad2. mammalian consists at least eleven subunits, most specific function still unknown. Apc2 contains cullin domain interacts another subunit, Apc11, RING-H2 finger domain. These might based on their similarity components ligase regulation, SCF (Skp1-cullin-F-box protein), responsible interaction rest ubiquitination system. other subunits remains obscure. Some contain protein-protein tetratricopeptide (TPR) motif. Two Apc3 Apc6, localised centrosome spindle. largest Apc1, shares motif unknown 19S cap proteasome. In articles upon this thesis we now Apc1 centromereassociated cells, it exists forms: soluble form associated centromere-bound form, may not components. We further both are bound isolated chromosomes, more than can observed immunofluorescence present chromosomes. likely recognised 3F3/2 antibody centromere. Apc8 localise interphase confirming presence cellular location. Polo-like kinase (Plk) specifically phosphorylate activate it, whereas A (PKA) suppresses activity. PKA superior Plk regulation expressed tissues types fairly constant levels relative other, they always perform functions part Their non-dividing suggests possibility additional outside