CellSig12 - 19 Flashcards Preview

Y2S2 - Cell Signalling > CellSig12 - 19 > Flashcards

Flashcards in CellSig12 - 19 Deck (19):
1

How is TGF-b involved in cancer?

Hypomorphic mutations frequently found in patients suffering - likely a tumour suppressor under normal conditions

2

What are microsatellites?

Repeated sequences that cause problems during DNA replication - can increase or decrease in length

3

Why are amorphic TGF-b mutations less dangerous?

Cancers use TGF-b later for angiogenesis and mesenchymal invasion transition

4

What is TGF-b precursor cleaved into?

TGF-b dimers (C-terminal), LAP (N-terminal)

5

What is LAP?

Latency associated protein

6

What is LAP tethered to?

EC matrix by LTBP

7

What is LTBP?

Latent TGF-b binding protein

8

What releases the LAP/TGF-b dimer complex from the EC matrix?

Proteases, and binding of thrombospondin to LAP

9

Characterise the TGF-b receptor structure

Enzyme linked - serine/threonine kinase domain

10

Outline the function of TGF-b receptors

Type II homodimer binds TGF-b dimer, recruiting and phosphorylating type I homodimer

11

How is lefty involved in TGF-b pathways?

Competes with TGF-b, but lack the alpha helix loop required for receptor dimerisation, so don't activate the pathway

12

How is bambi involved in TGF-b pathways?

Decoy receptors, resemble type I receptor, but lacks IC domain, forming inactive complex upon dimerisation with type II

13

Outline TGF-b signal transduction

Type I homodimer phosphorylates Smad 2 or 3, which then dimerises with Smad4, which then enters the nucleus as a TF

14

What are R-Smads?

All apart from 4, 6 +7, receptor-regulated Smads

15

What is special about Smad4?

Co-Smad - common to all TGF-b signalling

16

What anchors Smad to the PM?

SARA - Smad anchor for receptor activation proteins

17

What do Smads bind to in the nucleus?

HATs or HDCs - histone acetyltransferases or deacetylases

18

What are I-Smads?

Antagonists of TGF-b signalling - Smad 6 + 7

19

How do I-Smads work?

Bind activated type I receptor and activated R-Smads, blocking their activity