Molecular BIology of Cancer Topics             

Cell Cycle Overview

The molecular regulation of the cell cycle progression involves two major check points: G2/M and G1. A checkpoint is defined as a period in which information from many cellular processes (DNA synthesis, protein synthesis, growth signals, etc.) is integrated to determine whether or not to continue with the cell cycle. Different cyclings are active at different time periods during the cell cycle, thus controling the checkpoints and other processes (?).

There is an added level of complexity in the mammalian cell cycle because multiple cyclins and multiple cyclin-dependent kinases (cdc/cdks) function at discret points in the cell cycle.

At the G2/M checkpoint the cell determines if DNA synthesis has been compleated and the cell is ready to enter mitosis. This checkpoint has been well characterized in Xenopus laevis and in yeast. Early experiments discovered the activity of maturation promoting factor (MPF) is cyclical over the cell cycle progression, and that a injection of MPF a induced mitosis. Now we know MPF is comprised of p34/cdc2 and cyclin B.

Cyclin B protein levels increase during mitosis and rech their peak at the start of interphase. At this time, cyclin B is available to bind to and activate the cycling dependent kinase p34/cdc2. Cdc2 is then available to phosphorylate cytoskeletal proteins, making changes to the cellular scafold necessary for mitosis to occur (?).

After mitosis is over, cycling B is degraded and p34/cdc2 becomes inactive. Phosphorylation of Thr 161 by CAK (cdk-activating kinase) during interphase activates p34/cdc2 by allowing it to bind cyclin B. Even when bound to cyclin D, phosphorylation by Wee1/Myt of Thr14 and Tyr15 in the ATP binding pocket keeps p34/cdc2 inactive during S phase. When DNA replication is complete, the dual-specificity phosphatase cdc25 removes the inhibiting phosphates , and the cell enters mitosis.

At the G1/S checkpoint (Restriction point, R), Rb (retinoblastoma tumor suppressor protein) is phosphorylated by CDK2-cyclin D and CDK2-cyclin E.

Growth factor signaling is important at the G1 checkpoint, also known as the Restriction Point.

** incomplete **

subtitle

blah blah blah.

subtitle

blah blah blah.

Continue to "Genetics" or take a quiz: [Q1].

Need more practice? Answer the review questions below.

Questions under construction

Continue scrolling to answers below.

Hey! DON'T PEEK!!! Finish the questions fist!

Answers under construction