Control of cell proliferation

Question 1

Purpose of cell proliferation

Answer 1

Cell proliferation is required for development, particularly in the zygote after fertilisation and for growth and tissue development during embryogenesis.

Question 2

Regulation of cell proliferation

Answer 2

1) Cell number: control involves cell-cell communication, including growth factor signals and cell-cell contacts.
2) New cells must be identical: the cell cycle involves checkpoints and feedback control to maintain genome integrity.

Question 3

Phases of the cell cycle

Answer 3

1) G1 (growth) phase- occurs in response to an external signal, preparation for DNA replication.
2) S (synthesis) phase- DNA replication in the nucleus.
3) G2 (growth) phase- further growth and duplication of organelles.
4) M (mitosis) phase- chromosome segregation and cytokinesis (cell division).

Question 4

Checkpoints of the cell cycle

Answer 4

1) G1 checkpoint- ensures the cell is large enough to divide, enough nutrients are available to support daughter cells.
2) G2 checkpoint- ensures that DNA replication during S phase was successful.
3) Metaphase checkpoint- ensures that all chromosomes are attached to the mitotic spindle.

Question 5

Cyclin-dependent kinases (Cdks)

Answer 5

A group of enzymes that regulate checkpoint transitions during the cell cycle. They are themselves regulated by growth factors and proteins called cyclins.

Question 6

Cyclins

Answer 6

Activating molecules that fluctuate during the cell cycle, accumulating during interphase (G1, S, G2). By G2, enough cyclin is available to form M-Cdk (maturation promoting factor) complexes which initiate mitosis.

Question 7

Tumour suppressor genes

Answer 7

Sequences that inhibit transcription factors at certain cell cycle checkpoints if the cell is not ready to divide ie. growth factors absent, DNA damaged.

Question 8

Retinoblastoma protein (pRB)

Answer 8

pRB is a tumour suppressor gene regulating the restriction point at G1. In the absence of growth factors, pRB binds to transcription factors to inhibit cell proliferation. When growth factors are present, they target surface receptors, activating Cdks which phosphorylate and inactivate pRB.

Question 9

p53 tumour suppressor gene

Answer 9

p53 is a tumour suppressor gene regulating the DNA damage checkpoint between G1 and S. DNA damage increases p53 levels, activating a Cdk inhibitor called p21. This prevents continuation into the S phase, giving time for DNA repair. Severe DNA damage causes p53 to induce cell self-destruction by apoptosis.

Question 10

Consequences of checkpoint failure

Answer 10

• proliferation of cells in absence of growth factors
• replication of damaged DNA
• segregation of incompletely replicated chromosomes
• division of cells with wrong number of chromosomes (aneuploidy)
• genome instability=increased rate of mutation

Question 11

Oncogenes

Answer 11

Oncogenes are mutations along the growth factor signalling pathway that promote uncontrolled cell proliferation:

• receptors may be mutated to up-regulate gene expression in the absence of growth factors
• signalling proteins such as Ras may be faulty
• regulatory proteins such as transcription factors may be over-expressed

Question 12

Growth factors

Answer 12

Signalling proteins that stimulate cell growth, differentiation, survival, inflammation, and tissue repair. Their signal transduction is initiated by binding to membrane receptors on the surface of their target cells.