E8. Regulation of gene expression

Question 1

How does a cell change?

Answer 1

changing the synthesis and/or decay of specific proteins

Question 2

what is signal transduction

Answer 2

hormone binds to a receptor on the outside of the cell membrane and this causes changes on the inside of the cell

Question 3

what mediates switching in signal transduction?

Answer 3

phosphorylation and dephosphorylation
(one note for diagram)

Question 4

What is a kinase?

Answer 4

enzyme that adds a phosphate

Question 5

what is a phosphatase?

Answer 5

enzyme that removes a phosphate

Question 6

what is a signal transduction cascade?

Answer 6

-amplifies signal and carries it into the cell
-binding causes receptor kinase to activate (allosteric switch)
-Intracellular kinase activated by phosphorylation
-phosphorylation of target proteins

Question 7

Where could a cancer drug act to block or reduce receptor activation?

Answer 7

-Use an antagonist: a molecule that prevents activation of the receptor, it could be similar to the ligand
-Use an kinase inhibitor: a molecule that prevents the enzymatic activity of the receptor or downstream kinases, it could be similar to ATP

Question 8

how does signal transduction change cells?

Answer 8

changing gene expression

Question 9

Describe nuclear regulation

Answer 9

1. Regulation of transcription:
   main control mechanism of gene expression
   regulates the amount of pre-mRNA synthesised
2. Splicing:
   determines which parts of the pre-mRNA end up in the mRNA. Removing introns from pre-mRNA (one note for diagram)

Question 10

Describe cytoplasmic regulation

Answer 10

3. Regulation of translation:
   Determines how much protein is made from a particular mRNA and therefore the protein level
4. Regulation of mRNA degradation
   Determines how fast an mRNA is degraded and therefore the level of an mRNA (together with transcription)
5. Regulation of protein degradation
   Determines how fast a protein is degraded, and therefore the protein level

Question 11

as well as splicing, mRNAs require a cap structure where?

Answer 11

their 5’ end and a poly(A) tail at the 3’ end (capping and polyadenylation)

Question 12

Given a certain mRNA synthesis rate, what determines amount of a protein in the cell?

Answer 12

-mRNA degradation rate
-translation efficiency
-degradation rate of the protein

Question 13

what is splicing regulated by

Answer 13

RNA binding proteins and small RNAs which bind to introns

Question 14

what is mRNA specific translation regulation dependent on?

Answer 14

sequence specific RNA binding proteins or base pairing of microRNAs (miRNAs) being recruited to the mRNA

Question 15

what is mRNA decay mediated by?

Answer 15

sequence specific RNA binding proteins or by basepairing with microRNAs

Question 16

what are microRNAs (miRNAs or miRs)?

Answer 16

-20-22 nt RNA molecules that recognise a range of target mRNAs by base pairing.
-Expression of many microRNAs correlates with disease states: they are good BIOMARKERS for diagnosis

Question 17

why is it difficult for proteases to breakdown some proteins?

Answer 17

well structured domain. Therefore most degraded by ubiquitin-proteasome pathway

Question 18

Describe ubiquitin-proteasome pathway

Answer 18

-Multiple copies of the small protein ubiquitin are coupled to a lysine residue in the protein by specific ligases: polyubiquitination
-A large protein complex called the proteasome recognises the polyubiquitin chain, unwinds the secondary structure of the ubiquitinated protein and hydrolyses it into small peptides

Question 19

how is ubiquitin degradation linked to signal transduction?

Answer 19

by phosphorylation (one note)
-Ubiquitin ligases and the proteasome are targets for cancer treatment