regulation of transcription by cell signalling pathways Flashcards
cell signalling
by hormones/ growth factors
or by stressors such as dna damage,oxygen sensing, infection eg
Steroid hormone receptor
roles in intercellular signalling
physiological affects;
growth
tissue fevlopment
homeostatic control
key features of steroid hormone
membrane permeable
enter cell
bind to a receptor
receptor is a TF
hormone acts as ligand
signaling pathways of GR-mediated transcriptional regulationb
glucocorticoids enter cell
GR dissociates from chaperone proteins and enters nucleus
GR dimerises with another GR in nucleus
modulates gene transcription via direct interaction with cis-DNa elements
cross talk with other dna bound transcription factors
interaction with both dna elements and TFs
resulting modification leads to altered protein expression
other steroid receptors
some can be nuclear and bind to dna but do not activate transcription in absence of ligand
can repress transcription
modulated by ligand binding
can form homo or hetero dimers
hormone induced cell responses by cAMP
cAMP can regulate transcription via phosphorylation of CREB protein by PKA
this allows transcription to be controlled by hormones and other factors that regulate cAMP production
what does cAMP/CREB regulate
growth factor dependent cell proliferation and survival
glucose homeo stasis
cell differentiation
neuronal survival memory formation and addiction
TGF beta family
peptide molecules that regulate cellular processes
TGF beta
located in ECM
part of latent complex
injury = release of tgf b and binding to tgf b receptor type 2
type 2 phosphoprylates type 1 into heteromceric complexes
serine/theonine kinase activity of activated complex phosphorylates smad 2 and 3 to bind smad 4 and move to nucleus to enhance gene expression
JAK-STAT signalling
ligand binds receptor
receptors dimerise and phosphorylates tyrosine kinases on each other
kinases phosphorylate receptor
STAT 1 and 2 bind to cell and get phosphorylated
they dissociate and dimerise each other
STATS move to nucles and bind to DNA
tumour hypoxia
low oxygen tension
increases with increasing distance from capillaries
activated genes involved in angiogenesis,tumour cell migration and metastasis
molecular basis of hypoxia
hypoxia induces multipls things such as new blood vessels,red blood cells and anaerobic glycolysis
what regulates all these genes
HIF
hypoxia induced factor
HIF
TF regulates hypoxia induced gene transcription
heterodimer - hif1a and hif1b subunit
hif2a
regulated by o2 and degraded in normoxia, stabilised in hypoxia
hif a binding hif b
hypoxia - hifa stabilised
nuclear translocation
dimer formation
transcriptional activity
