Regulation of Gene Expression

Page
14

Movement of DNA within the genome: if it ends up near an active promoter, transcription may increase

Amplification of a proto-oncogene: increases the number of copies of the gene

Point mutations in the proto-oncogene or its control elements: causes an increase in gene expression

Slide 100

Tumor-Suppressor Genes

Tumor-suppressor genes help prevent uncontrolled cell growth

Mutations that decrease protein products of tumor-suppressor genes may contribute to cancer onset

Tumor-suppressor proteins

Repair damaged DNA

Control cell adhesion

Inhibit the cell cycle in the cell-signaling pathway

Slide 101

Interference with Normal Cell-Signaling Pathways

Mutations in the ras proto-oncogene and p53 tumor-suppressor gene are common in human cancers

Mutations in the ras gene can lead to production of a hyperactive Ras protein and increased cell division

Slide 102

Fig. 18-21

Receptor

Growth

factor

G protein

GTP

Ras

GTP

Ras

Protein kinases

(phosphorylation

cascade)

Transcription

factor (activator)

DNA

Hyperactive

Ras protein

(product of

oncogene)

issues

signals

on its own

MUTATION

NUCLEUS

Gene expression

Protein that

stimulates

the cell cycle

(a) Cell cycle–stimulating pathway

MUTATION

Protein kinases

DNA

DNA damage

in genome

Defective or

missing

transcription

factor, such

as p53, cannot

activate

transcription

Protein that

inhibits

the cell cycle

Active

form

of p53

UV

light

(b) Cell cycle–inhibiting pathway

(c) Effects of mutations

EFFECTS OF MUTATIONS

Cell cycle not

inhibited

Protein absent

Increased cell

division

Protein

overexpressed

Cell cycle

overstimulated

1

2

3

4

5

2

1

3

Slide 103

Fig. 18-21a

Receptor

Growth

factor

G protein

GTP

Ras

GTP

Ras

Protein kinases

(phosphorylation

cascade)

Transcription

factor (activator)

DNA

Hyperactive

Ras protein

(product of

oncogene)

issues

signals

on its own

MUTATION

NUCLEUS

Gene expression

Protein that

stimulates

the cell cycle

(a) Cell cycle–stimulating pathway

1

1

3

4

5

2

Slide 104

Fig. 18-21b

MUTATION

Protein kinases

DNA

DNA damage

in genome

Defective or

missing

transcription