Reg. of Seq. Specific DNA Binding Proteins (Ford L3)

Question 0

How does ligand binding affect sequence specific DNA binding proteins?

Answer 0

Ligand binding can alter the conformation of the binding protein to make it more or less able to bind to specific sequences

Question 1

List 5 ways sequence specific DNA binding proteins are regulated.

Answer 1

1. Ligand binding
2. Entry into Nucleus regulated
3. Amount of trxn factor in cell regulated
4. DNA binding regulated
5. Phosphorylation of DNA-binding protein

Question 2

How can sequence specific DNA-binding protein entry into the nucleus be regulated ?

Answer 2

steroid hormones can diffuse across cell membrane. once in cell can alter protein to allow it to enter nucleus (e.g. let go of a bound element). Thus will activate DNA-binding protein.

Question 3

What is calcineurin?

Answer 3

A protein phosphatase. Activates T-Cells. Dephosphorylates cytoplasmic NFATc (a trxn factor) to activate NFATc. Activated NFATc is then transported to the nucleus. Upregulates interleukin to stimulate growth of T-Cells.

Question 5

Explain the NF-kB pathway

Answer 5

Normally NF-kB bound in cytoplasm to IkB
“stimuli” phos. IkB –> IkB degraded
NF-kB diffuse into nucleus
NF-kB turns on inflammation response genes

Question 6

Wnt (canonical) pathway

Answer 6

Wnt (via cell surface receptors) turns off the Axin/APC/GSK complex
Beta-catenin no longer phosphorylated –> build up in cell
—> diffuse into nucleus and turn on cell growth and division (trxn)

Question 7

APC gene?

Answer 7

APC regulates many things…
in particular, APC (via complex with Axin/GSK) phosphorylates Beta-Catenin —> B-Catenin labeled for destruction
Mutation in APC –> Beta Catenin build up and upregulates trxn —> unchecked cell division and overgrowtn.