regulation of transcription factors I Flashcards
constitutive expression
normal gene expression
inducible expression
gene expression that needs stimulus from outside/inside the cell from hormones, GF, stress, infection
types of cell signalling
- endocrine signalling
- paracrine signalling
- autocrine signalling
- signalling by plasma membrane-attached proteins
- DNA damage, oxygen sensing, infeciton, temperature, nutrient deprivation
what are the various ways in which transcriptional activators or repressors can be recruited into action
- protein synthesis
- ligand binding
- protein phosphorylation
- addition of second subunit
- unmasking
- stimulation of nuclear entry
- release of membrane
role of steroid hormone receptor
roles in intercellular signalling
- physiological affects; growth, tissue development, homeostatic control
signalling pathways of GR-mediated transcriptional regulation
- following binding to glucocorticoids, cystolic GR dissociates from chaperone proteins such as Hsp90 & translocates into the nucleus.
- GR dimerises and modulates target gene expression via:
A. direct interaction with cis-DNA elements
B. cross talk with other DNA-bound TFs
C. interaction with both DNA elements and other TFs.
= modulation of target gene transcripts = altered protein expression.
process of action of steroid hormones
- membrane permeable
- enter cell
- bind to a receptor(s)
- this receptor is itself as a TF
- hormone acts a ligand
for GR change of sub-cellular localisation = induction of gene expression but what happens to other steroid receptors?
- some can be nuclear and bind DNA but don’t activate transcription in absence of ligand
- some can repress transcription
- in all cases , transcriptional properties are modulated by ligand binding
- can form heterodimers or homodimers
thyroid gland
horomone: TSH
response: thyroid homrone synthesis and secretion
adrenal cortext
hormone: adrenocorticotrophic hormone (ACTH)
response: cortisol secretion
what does cAMP do?
cyclic AMP
- can regulate transcription via phosphorylation of CREB (cAMP regulatroy element binding) protein by PKA (cAMP dependent protein kinase)
what does cAMP allow for?
allows transcription to be controlled by hormones and other factors that regulate cAMP production
what does PKA also do?
phosphorylates cytoplasmic proteins
what biological functions does cAMP/CREB signalling pathway regulate?
- growth factor-dependent cell prolif. and survival
- glucose homeostasis
- cell differentiation (Tcells, hepatocytes, spermatocytes)
- neuronal survival, memory formation, addiction
transforming growth factor B superfamily
peptide molecules that regulate a wide array of cellular processes such as cell growth, cell differentiation, cellular homeostasis and development
what is BMP?
bone morphogenetic protein
what is ALK?
activin-like kinase receptor
process of recruitment of TGFb R-SMADS to promoters
a. mesoderm formation and left right axial structure in early embryonic development by induction of activin-responsive target genes
b. inhibition of cell growth
c. promotion of cell cycle exit and differentiation
d. repression of cell type specific transcription
JAK-STAT process
- binding of interferon cross-links adjacent receptors and Jaks cross phosphorylate each other on tyrosines
- activated Jaks phosphorylate receptors on tyrosine
- after STATs dock on specific phosphotyrosines on the receptor, the Jaks phosphorylate them
- STATs dissociate from receptor and dimerise via SH2 domain
- STATs migrate to nucleus bind to DNA and other gene regulatory proteins
interferon y
macrophage activation; increased MHC protein expression
interferon a
increased cell resistance to viral infection
IL10
inhibits synthesis of proinflammatory cytokines
leptin
stimulates the synthesis of a-melanocyte-stimulating hormone (a-MSH) to inhibit appetite
IL6
promotes immune response
