Genomics #3 Transcription Regulation2.txt
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Name some ways transcriptions factors can be regulated:
De/phosphorylation, de/hydroxylation, un/binding of ligands, un/cleaving of proteins, presence/absence of (lipids, proteins, ions, etc.) and many more
B-Catenin is part of which signaling pathway? How is B-Catenin regulated?
Wnt signaling pathway, Phosphorylation and Degradation
The Wnt/B-Catenin pathway regulates at least ____ genes that it can up-regulate.
The Wnt/B-Catenin pathway regulates aspects of development such as?
Regulates cell-cell interaction during embryogenesis, Cell proliferation, differentiation, Abnormal signaling occurs in some cancers
What are the kinases involved in the "degradation complex?"
APC, axin, casein kinase 1 (CK1), and Glycogen Syntase Kinase 3 (GSK3).
Which kinases phosphorylate B-Catenin? What happens next?
CK1 and GSK3, B-Catenin gets ubiquitylated and degraded by the proteasome.
what is the co-repressor that is bound to LEF1/TCF to suppress transcription?
What happens to B-Catenin in the absence of Wnt?
it gets degraded
How is B-Catenin released in the presence of Wnt to stimulate transcription?
Wnt binds to the receptor "frizzled" and co-receptor LRP, this leads to recruitment and activation of "dishevelled", then the "degradation complex" is recruited and CK1 and GSK3 can phosphorylate the LRP, the complex falls apart and B-Catenin is no longer phosphorylated and can enter the nucleus.
Once in the nucleus, how does B-Catenin stimulate transcription?
B-Catenin will bind to the LEF1/TCF, displacing Groucho, and inducing transcription of various genes
What is the function of STAT?
Provide a direct link between signal transduction across the cell membrane and transcription
Where are STATs found in the absence of ligand? What is there state?
in the cytosol, in an unphosphorylated state
T/F: STAT phosphorylates JAKs.
False, it's the opposite
If ligand binds to JAK, what is the pathway that follows?
The 2 JAK come together to cross-phosphorylate each other leading to the recruitment of STATs. STATS bind to JAKs, get phosphorylated, STAT is freed and dimerizes with another STAT in the cytosol, enters the nucleus to bind a particular DNA sequence and activate transcription.
What happens when EGF binds the receptor?
EGF cross phosphorylate, recruiting proteins Grb-2/Sos, the complex recruits inactivated-Ras which is bound to GDP, Ras is released, binds to GTP, then activated leads to activation of Raf1K-->MEK1/2-->ERK1/2 which is part of the MAP kinase pathway.
What do the MAP Kinase family pathways lead to?
The promotion of growth and diffentiation
ERK, JNK, and p38 are part of what pathway?
Map Kinase family pathway
What are the three examples of transcription factors that are phosphorylated by ERK1/2 or RSK?
Once phosphorylated by _______ Fos combines with______ to form __________ transcription factor complex.
ERK 1/2, transcription factor-Jun, Activator Protein-1 (AP-1)
Fos binds to the DNA sequence ___________.
What does the phosphorylation of Fos by ERK1/2 do?
increases its ability to activate of transcription.
What does phosphorylation of Myc do?
Myc, and Max bind to an __________ on the DNA. What can result from this step?
E-Box (CAC(A/G)TG), can activate/repress transcription, or it can interact with other proteins like Miz1 to repress transcription of some genes.
What happens when CREB is phosphorylated by ERK1/2 or RSK?
CREB can phosphorylate a number of kinases, it can lead to the the binding of the CREB, which recruits RNA-Polymerase-II complex promoting transcription
CREB, when _________ can bind to CRE _______.
What are some (4) situations that can activate NF-kB?
Times of cell stress, Inflammation, Activation of certain parts of the innate immune system, Development
What are some ligand/receptor interactions that can activate NF-kB?
Activators of Toll-like receptors, TNF-a, IL-1, Others
The inactivated transcription factor, NF-kB is held ___________ by ________.
in the cytosol, IkB
what results in the activation of IKK?
IKK phosphorylates IkB which is the signal to be ubiquinated followed by degradation, which frees NFkB that translocates to the nucleus to initiate transcription.
What is the name of the receptor that is able to initiate transcription from the binding of a hydrophobic ligand? How many are there?
Nuclear Receptor Superfamily, 48
The Nuclear Receptor Superfamily has ______ binding domains, __________ and _________.
(2), Dna binding domain, and the ligand binding domain
Explain the differences of the (2) classes of Nuclear Receptor Superfamily Members.
- Class 1 = in inactive form, they are often found in cytoplasm
- Class 2 = inactive form, they are found in the nucleus
What are some examples of Nuclear Receptor Superfamily Members?
- GR = Glucocorticoid Receptor
- ER = Estrogen Receptor,
- RAR = Retinoic Acid Receptor,
- TR = Thyroxine Receptor,
- VD3R = Vitamin D Receptor
PPARs are a member of what class of Nuclear Receptor Superfamily? Name the 3 main members?
Class 2, PPAR alpha, beta/delta, and gamma
When class 2 PPARs bind ligands, they interact with other ______ members, then they bind to the DNA sequence ___________ to affect ________________.
RXR, Peroxisome Proliferator Response Element (PPRE), Affect the transcription of genes involved in regulating various nutritional pathways and energy homeostasis
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