Signal transduction Flashcards
1
Q
STR superfamily
A
- steroid-thyroid-retinoid
- lipid soluble hormones
- longer time to see effects but action is longer lasting
- involved in: development, differentiation, cell to cell interaction, nutrient sensing, xenobiotic sensing
2
Q
Similarities in STR receptor superfamily
A
- DNA binding domain⇒ 2 zink fingers
- HRE ⇒ same nucleotide sequence for different receptor monomers, but spacing different
- Ligand binding domain ⇒ close to C terminal
- C terminal ⇒ associated with HSP binding and transactivators
- D region ⇒ hinge region for protein
- 2 transactivator domains ⇒ AF1 and AF2
- A/B region ⇒ coactivators, transactivators, transcription proteins
3
Q
Type 1 receptor superfamily
A
- ligand binding ⇒ results in dissociation of heat shock proteins, homo-dimerization, translocation, binding of HREs
- include androgen receptor, estrogen receptor, glucocorticoid receptor, progesterone receptor and mineraocorticoid receptor
4
Q
Mechanism of Type 1 receptor
A
hormone ⇒ NR/HSP complex in cytoplasm ⇒ NR/hormone complex + HSP ⇒ NR dimer ⇒ through nuclear pore ⇒ + coactivators ⇒ bind to HRE in DNA ⇒ mRNA ⇒ protein
5
Q
Type 2 receptor superfamily
A
- retained in nucleus regardless of ligand binding status and in addition bind as heater-dimers to DNA
- often complexed with corepressor proteins (absence of ligand)
- ligand binding ⇒ dissociation of corepressor and recruitment of coactivator protein + RNA polymerase
- no HSP association
- include retinoic acid receptor, retinoic X receptor and thyroid hormone receptor
6
Q
Special features of transcription factors of receptors
A
- Alpha-helices
- helix-turn- helix
- helix-loop-helix
- leucine zipper
- Zn finger
7
Q
Zinc finger
A
small protein structural motif that is characterized by the coordination of one or more zinc ions in order to stabilize the fold
8
Q
Steroid type receptor
A
- located in cytoplasm + associated with HSP until ligand bind ⇒ translocate
- long A/B domain
- do not bind to HRE unless ligand binds
- display repressor effects
must dimerize in order to bind to HRE - agonist/antagonist binding site is different
9
Q
Thyroid type receptor
A
- short A/B domain
- no heat shock protein association
- bind to HRE without ligand + can bind as monomers
- complex with corepressor proteins
10
Q
Hormone resistance syndromes and disease association
A
- Glucocorticoid resistance ⇒ hypercortisolism without Cushing symptoms
- Mineralocorticoid resistance ⇒ pseudohypoaldosteronism
- Androgen resistance ⇒ testicularis feminisatio
- D-vitamin resistance ⇒ rickets
- ER overproduction ⇒ breast cancer
- AR overprod. ⇒ prostate cancer
- GR detection ⇒ leukemias, lymphoid tumors, uterus tumors
11
Q
Antiestrogens
A
- e.g. Tamoxifen
- do not dissociate + cause inhibition of dimer formation
- compete for hormone binding site
- bind to receptors, enter cell but do not bind coactivators ⇒ genetic translation not affected
12
Q
Hypoxia inducible factors (HIFs)
A
- transcription factors, respond to changes in available oxygen in cellular environment
- HIF-1 ⇒ heterodimer of alpha and beta subunit(ARNT)⇒ upregulates genes to promote survival in low-oxygen conditions
- HIF signaling cascade mediates effect of hypoxia
- vital to development
13
Q
Hypoxia
A
- keeps cells from differentiating
- promotes formation of blood vessels
- important for formation of vascular system in embryos and cancer tumors
- promotes migration of keratinocytes + restoration of epithelium
14
Q
HIF-1
A
- part of basic helix-loop-helix protein eukaryote transcription factor super gene family
- HIF1a/HIF1b heterodimer in every tissue
- HIF-1a inducible oxygen sensitivie
- HIF-1b oxygen insensitive
- HIF-1a increased in hypoxia within minutes
- HIF-1a increased in malignant tumors
15
Q
Receptor Tyrosine kinase
A
- high-affinity cell surface receptors for many polypeptide growth factors, cytokines and hormones
- can activate G protein linked pathway
- vital in differentiation and proliferation of many cell types
- ligand binds⇒ dimerisation ⇒ autophosphorylation⇒ intracellular domain activate signal transduction pathway
