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 S-phase 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.