Lecture 13: Other pathways

Question 1

Wnt ligands

Answer 1

acts as paracrine and autocrine

palmitoylation signal sequence of 15 to 30 amino acids is required for transport of Wnt across membrane

mutation of cysteine or removal palmitate inactivates Wnt

Question 2

Porcupine (Por)

Answer 2

Palmitoylation of Wnt ligand and move from ER to golgi

Question 3

Wingless (Wls)

Answer 3

helps to transfer Wnt ligand from golgi to plasma membrane

Question 4

2 types of receptor in Wnt signalling

Answer 4

LRP

Frizzled

Question 5

Activated B-catenin

Answer 5

transcription factor

binds to LEF-1/TCF

displaces groucho for transcription

Question 6

Phosphorylation of B-catenin

Answer 6

kept at off state by ubiquitination of B-TrCP (E3-ligase) and destruction complex

sent to proteasome for degradation

Question 7

3 components of destruction complex

Answer 7

1. Active GSK-3B
2. Axin
3. APC

binds to phosphorylated B-catenin

Question 8

Dishevelled

Answer 8

activated form inactivates GSK-3B to prevent B-catenin phosphorylation

inhibit destruction complex

Question 9

APC and familial adenomatous polyposis (FAP)

Answer 9

hundred of polyps in the colon and rectum

truncations in APC (inactivates destruction complex)

aberrant activation of Wnt pathway

increase cell proliferation and adenomatous lesions

Question 10

Importance of hedgehog signalling

Answer 10

central to embryonic development of all tissues

mutations have been implicated in birth defects such as cyclopia (single eye)

and multiple form of cancer

Question 11

3 types of hedgehog ligand

Answer 11

1. Sonic hedgehog (sHh)
2. Indian hedgehog (iHh)
3. Desert Hedgehog (dHh)

Question 12

Hedgehog signalling is closely associated with?

Answer 12

primary cilium

• microscopic sensory signalling
• cells in vertebrate tissues use primary cilium to gather information about their environment

Question 13

2 types of hedgehog receptor

Answer 13

1. Patched (Ptc)

2. Smoothened (Smo)

Question 14

Intact Gli and cleaved GliR

Answer 14

Cleaved (GliR) by Slimb: binds to corepressor in nucleus, no transcription

Intact: bind to CREB binding protein (CBP) and activates transcription

Question 15

Mutations in PTCH1

Answer 15

negative regulator

basal cell carcinomas (BCC), hyperactive Hh pathways

medulloblastoma

rhabdomyosarcoma (muscle tumor)

Question 16

Types of Notch receptors

Answer 16

Notch 1-4

single-pass transmembrane protein

Question 17

5 Notch ligands

Answer 17

Delta-like ligand 1, 3, 4 (DLL 1,3,4)

Jagged 1,2 (JAG 1,2)

Question 18

3 domains of Notch receptor

Answer 18

extracellular (NECD)

transmembrane (TM)

intracellular (NICD)

Question 19

Notch 1 activating mutation can be identified in what tumor?

Answer 19

In over 50% of T-cell acute lymphoblastic leukemia (T-ALL)

Question 20

Gamma-secretase inhibitor

Answer 20

inhibit the release of NICD from TM through cleavage

only notch signalling inhibitor in clinical trial