Escherichia coli

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Escherichia coli LPS/O antigens, OMPs,
flagella, peptidoglycan, inner membrane, DNA,
ribosomes, tRNA, various protein assemblies
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• The Cell Cycle
• 11.1 The Cell Cycle Discovery of the Gap Phases
• 11.2 Events in Mitosis Prophase, Prometaphase,
  Metaphase
• Anaphase, Telophase Cytokinesis
• How Do Chromosome Move during Mitosis?
• Mitotic Spindle Forces A Kinetochore Motor
• 11.3 Control of the Cell Cycle
• The Discovery of Cell-Cycle Regulatory Molecules
• MPF Contains a Protein Kinase and a Cyclin
• Cell-Cycle Checkpoints
• 11.4 Cancer Out of Control Cell Division
• Cancer Involves Loss of Cell-Cycle Control

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• During the gap phases, organelles replicate and
  more cytoplasm is made. Cells perform all their
  normal cell functions during G1 phase, which is
  highly variable in length.

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Prometaphase

• As chromosomes condense, the nucleolus
  disappears and the nuclear envelope breaks down.
  Spindle fibers attach to each sister chromatid at
  kinetochores located at the centromeres.
  Kinetochore microtubules now start moving
  chromosomes toward the middle of the cell (Figure
  11.9, part 2).

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Cytokinesis in animals, fungi, and slime molds
occurs when a ring of actin and myosin filaments
contracts inside the cell membrane, causing it to
pinch inward in a cleavage furrow
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A Kinetochore Motor

• Dyneins and other kinetochore motor proteins
  appear to detach near the chromosome and reattach
  to the kinetochore microtubule farther down its
  length, causing the microtubule shortening
  responsible for pulling chromosomes to opposite
  poles of the cell (Figure 11.13).

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Fig. 4.12
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• M-phase promoting factor (MPF) is present in the
  cytoplasm of M-phase cells and induces mitosis
• MPF is composed of two distinct subunits a
  protein kinase that catalyzes phosphorylation of
  a target protein by ATP, and a cyclin.
• The concentration of the MPF protein kinase does
  not change much during the cell cycle but the
  concentration of MPF cyclin increases during
  interphase, then peaks in M phase before
  decreasing again.
• The MPF protein kinase is a cyclin-dependent
  kinase (Cdk) that is active only when it is bound
  to the cyclin subunit. Thus, when cyclin
  concentrations are high, more MPF is active and
  the target proteins are phosphorylated, causing
  the initiation of mitosis

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MPF is synthesized in an inactive phosphorylated
form. Late in G2 phase, enzymes dephosphorylate
cyclin to activate MPF for phosphorylation of
many different types of proteins
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A cell-cycle checkpoint is a critical point in
the cell cycle that is regulated. Tumor
suppressor proteins can also stop the progression
at specific checkpts.
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Cancer Out of ControlCell Division

• Cancer is a common, often lethal disease that
  affects many humans and other animals. Despite
  their differences, all cancers derive from cells
  in which cell-cycle checkpoints have failed
  generally starting with defects in the G1
  checkpoint.
• A tumor forms when one or more cells in a
  multicellular organism begins to divide
  uncontrollably. Benign tumors are noninvasive,
  but malignant tumors are invasive and can spread
  throughout the body via the blood or lymph and
  initiate new tumors.
• Detachment from the original tumor and invasion
  of other tissues is called metastasis.

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Liver metastases from a Colon Cancer
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Social Control

• Unicellular organisms pass the G1 checkpoint
  when nutrients are available and cell size is
  sufficient. Cells of multicellular organisms
  respond instead to signals from other cells, so
  that cells divide only when their growth benefits
  the whole organism. This is known as social
  control.
• Normally, mammalian cell cultures will not grow
  unless growth factors are present. Cells release
  these polypeptides or small proteins to signal
  other cells to grow. There are many different
  growth factors. Different types of cells divide
  in response to different combinations of growth
  factors, which must be present for the cell
  culture to grow.
• Cancer cells, however, divide without growth
  factors. They are no longer subject to social
  control at the G1 checkpoint.
• Growth factors initiate cell division by
  triggering cyclin synthesis. The cyclin then
  activates a cyclin-dependent kinase (Cdk) that
  activates the S-phase proteins

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In some human cancers, the G1 cyclin is always
overproduced, permanently activating Cdk, which
then continuously phosphorylates its target
proteins. Either the presence of excessive
growth factors or cyclin production in the
absence of growth factors can cause cyclin
overproduction.
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Involvement of Retinoblastoma Protein in
Regulation
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Cancer Is a Family of Diseases

• Many different types of defects can cause the G1
  checkpoint to fail. Most cancers result from
  multiple defects in cell-cycle regulation. Each
  type of cancer is caused by a unique combination
  of errors.