Protein Control

• Cytoskeleton


  Complex network of protein filaments that gives mechanical support and shape to cells
• Cytoskeleton


  • Consists of different protein structures including microtubules, which are found in all eukaryotic cells
• Microtubules


  Hollow cylinders composed of the protein tubulin, that radiate from the microtubule organising centre (MTOC) or centrosome
• Microtubules


  • Control the movement of membrane-bound organelles and chromosomes, and form the spindle fibres active during cell division
• Formation and breakdown of microtubules

  Involves polymerisation and depolymerisation of tubulin
• Cell Cycle


  Consists of interphase and mitotic (M) phase
• Interphase


  Involves growth and DNA synthesis including G1, S, and G2 phases
• Mitotic Phase


  Involves mitosis and cytokinesis
• Mitosis


  Consists of prophase, metaphase, anaphase and telophase
• Prophase


  • DNA condenses into chromosomes, nuclear membrane breaks down, spindle microtubules extend and attach to chromosomes
• Metaphase


  • Chromosomes are aligned at the metaphase plate
• Anaphase


  • As spindle microtubules shorten, sister chromatids are separated and chromosomes are pulled to opposite poles
• Telophase


  • Chromosomes decondense and nuclear membranes are formed around them
• Checkpoints


  Mechanisms within the cell that assess the condition of the cell during the cell cycle and halt progression to the next phase until certain requirements are met
• Cyclins


  Proteins that accumulate during cell growth and are involved in regulating the cell cycle
• Cyclin-dependent kinases (CDKs)


  Combine with cyclins to form active cyclin-CDK complexes that phosphorylate proteins to regulate progression through the cell cycle
• G1 Checkpoint


  • Retinoblastoma protein (Rb) acts as a tumour suppressor by inhibiting transcription of genes needed for DNA replication, until phosphorylation by G1 cyclin-CDK inhibits Rb
• G2 Checkpoint


  • Assesses success of DNA replication and DNA damage, with p53 protein able to stimulate repair, arrest the cell cycle or cause cell death
• Metaphase Checkpoint


  • Controls progression from metaphase to anaphase, halting progression until chromosomes are aligned correctly on the metaphase plate and attached to spindle microtubules
• Uncontrolled reduction in cell cycle rate

  May result in degenerative diseases (e.g. Alzheimer's disease)
• Uncontrolled increase in cell cycle rate

  May result in tumour formation
• Proto-oncogene


  A normal gene, usually involved in the control of cell growth or division, which can mutate to form a tumour-promoting oncogene
• Apoptosis

  The death of cells which occurs as a normal and controlled part of an organism's growth or development (Programmed cell death)
• Apoptosis


  • Is triggered by cell death signals that can be external or internal
• External Death Signals


  • Production of death signal molecules from lymphocytes that bind to surface receptor proteins and trigger a protein cascade
• Internal Death Signals


  • DNA damage that causes activation of p53 tumour-suppressor protein
• Both external and internal death signals result in the activation of caspases that cause the destruction of the cell
• Apoptosis is essential during development of an organism to remove cells no longer required as development progresses or during metamorphosis
• Cells may initiate apoptosis in the absence of growth factors