Lecture 4.  Cell Cycle Control and Cancer

I. Control of the Cell Cycle

The central components of the cell-cycle control system are enzymes known as cyclin-dependent kinases or Cdks. Like other protein kinases, Cdks catalyze the covalent attachment of phosphate to protein substrates, resulting in changes in the substrate's enzymatic activity or its interaction with other proteins.

Cdk activities rise and fall as the cell progresses through the cell cycle. These oscillations lead directly to cyclical changes in the phosphorylation of key components of the cell-cycle machinery, resulting in the initiation of cell-cycle events.

Cyclin: any of a family of structurally related proteins that bind to and activate cyclin-dependent kinases (Cdk); originally discovered as proteins whose concentration varies with the phase of the cell cycle.

 G1 cyclins: cyclins whose concentration depends on the rate of cell growth or on growth-promoting signals rather than on the phase of the cell cycle, and that activate Cdks that stimulate entry into a new cell cycle at the end of G1.

G1/S cyclins: cyclins whose concentration rise at the G1/S boundary and that activate Cdks responsible for initiation of DNA synthesis.

M cyclins: cyclins whose concentration rises at the approach to mitosis and that activate Cdks necessary for entry into mitosis.

S cyclins: cyclins whose concentrations rise and remain high during S phase, when they activate Cdks necessary for DNA synthesis, and G2 phase, when they are required for other processes.

II.  Cancer

What is Cancer?

            A diverse class of diseases marked by abnormal cell proliferation, due to the loss of cell
            cycle control.

    A.  Characteristics of Cancer cells.

        1.  Unlimited cell division.

                i.e.  Hela cells...

        2.  Cancer characteristics are passed to progeny.

        Cancer-family syndromes:  Family members seem to inherit a nonspecific predisposition toward
        tumors of various types.

        3.  Cancer cells can metastasize.

            Tumor:  a mass of abnormal cells within an otherwise normal tissue.

            Benign tumor:  The abnormal cells remain at the original site.

            Malignant tumor:  Tumor cells not only continue to proliferate, but also spread beyond their
            original site and invade nearby tissues by a process called metastasis.

            Metastasis:  The spread of cancer cells beyond their original site through blood or lymph
            vessels and start new centers of uncontrolled cell growth wherever they go, bring about unusual
           numbers of chromosomes cease to function in any constructive way, and they also lose their
           attachments to neighboring cells.