Cell signalling 4

What is the structure of nuclear receptors?

Contains N-terminal domain and activator function 1 which interacts with co-regulator proteins

DNA binding domain

Hinge region

Ligand binding domain with activator function 2

How do nuclear receptors function?

Translocate to the nucleus

bind to regions on DNA to activate/repress genes

What is oestradiol?

Steroid derived from cholesterol

primarily in ovaries by aromatase

dominant oestrogen

What is oestrogen mechanism?

Binds to ERs on chaperone proteins

ERs dissociate from chaperone proteins

ER homodimers

exposure of nuclear localisation sequence and translocation to nucleus

What is the connection of oestradiol to breast cancer?

CYP19 expressed in breast tissue produces oestradiol

Normally low levels, tumours express at higher levels

Oestradiol can enhance CYP19 expression

What is the mechanism of thyroid hormones?

Thyroid hormones (T4/T3) enter cell by thyroid hormone transporters

metabolised by deiodinase enzymes

T3 binds to TR with retinoid acid receptor (RXR)

Without T3 TR-RXR is repressed by corepressors

T3 binding causes loss of corepressors and transcription of thyroid hormone genes