Molecular Oncology I and II

Question 1

Signal transduction

Answer 1

regulate the ability of a cell to change its behavior in response to stimuli/receptor-ligand interaction

1. Signal: primary messenger
2. receptor: specificity
3. Intracellular signaling pathway: second messenger (cAMP, Ca2+), kinases/phosphatases, G-proteins
4. cellular response: altererd gene expression or protein function
5. termination
6. regulation

Question 2

cell-surface receptors

Answer 2

G-protein coupled receptors:
receptor tyrosine kinases (RTKs)
cytokine receptors

Ion-channel-coupled receptors

Question 3

Intracellular receptors

Answer 3

nuclear and cytosolic receptors: transcription factors, hormone (androgen receptor, f.ex)

Other receptors: other gasses, ROS, DNA

Question 4

cellular stress responses

Answer 4

Cells encounter various stress signals included exogenously as well as endogenously all the time

various intracellular signaling pathways are activated in resopnse to stress signals and might have different outcomes in different cells

some proteins/signling pathways play a more vital role in cellular stress responses, and is often activated/mutated in cancer

complexx stress signaling ensures survival of healthy cells an dremoval of potential dangerous/damaged cells during sterssful conditions

examples of cellular stresses:
UV, chemicals, ionizing radioation, pathogens, DNA damage, ROS

examples of stress responses:
cell cycle arrest, (DNA) repair, antioxidant, senescence, apoptosis

Question 5

Kinases, phosphatases and G proteins in cell signaling

Answer 5

Protein kinases add phosphate gropus to the OH group on tyrosine or serine/threonine residues of one or more target proteins

protein phosphatases remove phosphate groups

GTP-binding proteins (G-proteins) is a GTPase superfamily. bound GTP when “on”, causing downstream signling. has GDP when “off”. trimeric G-proteins = GPCR
Monomeric G proteins: Ras

Question 6

Example: GPCRs regulating adenylyl cyclase

Answer 6

G-alpha-s-GTP activates AC (adenylyl cyclase) that synthesizes 2nd messenger cAMP (GPCR activates AC)

inactive protein kinase A (PKA) is a tetramer with 2 regulatory and 2 catalytic subunits

binding of cAMP to R subunits of PKA releases active C subunits

activated PKA C subunit phosphorylates many substrates

the activated PKA C subunit translocates into the nucleus and phosphorylates the TF CREB (CRE-binding protein)

phosphorylated CREB binds to target genes via a specific DNA sequence: cAMP-response element (CRE)

Co-activator CPB/P300 links CREB to the basal transcription machinery, allowing transctiprion of target genes.

e.g. hormone-stimulated glycogen breakdown