Transcript Freeman 1e: How we got there

Escherichia coli – LPS/O antigens, OMPs, flagella,
peptidoglycan, inner membrane, DNA, ribosomes,
tRNA, various protein assemblies
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
•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.
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).
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
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).
Fig. 4.12
• 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
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
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.
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.
Liver metastases from a Colon Cancer
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 Sphase proteins
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.
Involvement of Retinoblastoma Protein in Regulation
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.