Ch 10: Cyclins and Cyclin-Dependent Kinases (CDKs)

evidence for cytoplasmic signals

• molecules present in the cytoplasm

  • regulate progress through the cell cycle

experiment 1 evidence for cytoplasmic signals

when a cell in the S phase was fused with a cell in G1, the G1 cell immediately entered the S phase—DNA was synthesized

experiment 2 evidence for cytoplasmic signals

when a cell in the M phase was fused with a cell in G1, the G1 cell immediately began mitosis—a spindle formed and chromatin condensed, even though the chromosomes had not been duplicated

conclusion evidence for cytoplasmic signals

the results of fusing cells at two different phases of the cell cycle suggest that molecules present in the cytoplasm of cells in the S or M phase control the progression of phases

what are the two groups of intracellular molecules that regulate the cell cycle?

1. positive regulators

2. negative regulators

positive regulators

promote movement to next step of the cell cycle

negative regulators

stop advancement of the cell cycle

kinases

transfer phosphate groups

cyclins and cyclin-dependent kinases (CDKs)

• levels of these proteins fluctuate predictably over the cell cycle

• internal and external signals can trigger increases in cyclin levels

• cyclins are degraded by cytoplasmic enzymes

cyclin

protein

are both cyclins and CDKs necessary for the cell cycle?

yes

true or false. kinases activate each other.

true

how positive regulators work

• only active when bound to CDKs and specifically phosphorylated

• CDK levels are stable throughout cycle

  • regulation dependent on levels of cyclin

true or false. the activity of cyclins and CDKs fluctuate during the cell cycle.

true

1

synthesis of cyclin begins in late S phase and continues through G2. because cyclin is protected from degradation during this stage, it accumulates

2

accumulated cyclin molecules combine with recycled CDK molecules, producing enough molecules of MPF (mitosis promoting factor) to pass the G2 checkpoint and initiate the events of mitosis

3

MPF promotes mitosis by phosphorylating various proteins. MPF’s activity peaks during metaphase

4

during anaphase, the cyclin component of MPF is degraded, terminating the M phase. the cell enters the G1 phase

5

during G1, conditions in the cell favor degradation of cyclin, and the CDK component of MPF is recycled

negative regulatory molecules

• CDKs inhibitors monitor particular events (block binding)

• other negative regulators stop cell cycle in other ways

  • the best understood are retinoblastoma protein (Rb), p53, p21

  • act primarily at G1 checkpoint

cancer and the cell cycle

• uncontrolled cell growth

• no negative regulation, only positive

  • negative regulation may be disrupted through mutation

• begins with a gene mutation that results in a faulty protein that regulated cell production

tumor

reproduction of mutated cells surpasses growth of normal cells

what cell actions cause a tumor?

increase cell division with normal apoptosis and normal cell division with decreased apoptosis

proto-oncogenes

• potential to be oncogenes

• normal genes that code for positive cell cycle regulators

• when mutated they can become oncogenes