Brainscape's Knowledge GenomeTM

Browse over 1 million classes created by top students, professors, publishers, and experts.


See full index

P&R > Nuclear signaling > Flashcards

Nuclear signaling Flashcards

1
Q

steroid hormone signaling classes depend on what two factors

A

where they are located and how they bind DNA

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
2
Q

Name the subclass of the nuclear receptor superfamily that bind ligand in cytosol and DNA as homodimer and two ligand members

A

steroid hormone receptors (glucocorticoid, estrogen, androgen, and progesterone)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
3
Q

When are steroid hormone receptors translocated to the nucleus?

A

After they have bound their ligand, they undergo a conformational change and subsequent translocation

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
4
Q

Domains of SHR family (3)

A

Conserved DNA binding domain (DBD w/ Zn fingers), flexible hinge and moderately conserved ligand binding domain at C-terminus

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
5
Q

How does SHR affect gene regulation?

A

SRs dimerize after ligand binding, recognize regulatory elements in target genes called Hormone responsive elements.

Also, SRs can activate genes without HREs through interactions with other proteins (ex STATs)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
6
Q

SHR signaling pathway overview (3 step)

A
  1. Hormone enters cell by passive diffusion and binds receptor.
  2. SR released from HSP chaperone, translocates to nucleus
  3. Inside nucleus, receptor dimerizes and binds
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
7
Q

T/F. Steroid hormones only enter cell through simple diffusion.

A

False, though mostly this is the case, there is some evidence that they can be actively taken up by endocytosis of carrier protein bound hormones

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
8
Q

Two types of SH ligands

A

Full and partial (partial AKA SERMs, for selective estrogen receptor modulators).

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
9
Q

T/F. Binding of partial agonists to SHRs won’t result in release from heat shock proteins

A

False, it will result in conformational change and release from HSPs

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
10
Q

Pathways which originate from outside nucleus and move in to affect gene regulation (5)

A

Steroid hormone signaling, notch signaling, NK-kB signaling, Wnt signaling, Shh

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
11
Q

Three groups of SHRs based on their unliganded distribution in the cell

A

ERs found in nucleus, GR/AR in cytoplasm, MR/PR have mixed distributions over both

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
12
Q

Where in the cell does the majority of SHR dimerization occur?

A

Nucleus, so happens post ligand binding

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
13
Q

How does SHR phosphorylation regulate function?

A

Nuclear export, shuttling/synergy/turnover, etc

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
14
Q

Notch signaling pathway impacts

A

Cell proliferation, differentiation and apoptosis - stem cell regulation, development

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
15
Q

Notch signaling ligand families (2)

A

Jagged and Delta family

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
16
Q

T/F. Notch signaling involves cell-cell communication

A

True, ligands reside on plasma membrane of one cell, while notch receptor is in plasma membrane of second cell

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
17
Q

Regulatory points of notch signaling (4)

A
  1. Ligand ubiquitination and endocytosis
  2. gamma -secretase (S3 cleavage)
  3. ADAM S2 cleavage
  4. Furin cleavage (S1)
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
18
Q

How does furin cleavage affect Notch protein?

A

Newly translated Notch undergoes Furin cleavage, fringe glycosylation is transported to cell surface

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
19
Q

How does Delta/Jagged endocytosis affect Notch regulation?

A

Pulls on Notch which exposes site-2 (S2), which is then the site of cleavage by ADAM

20
Q

Where does gamma-secretase bind, and what does it release?

A

Cleaves site 3 to release NICD

21
Q

Where does gamma-secretase bind, and what does it release?

A

Cleaves site 3 to release NICD, which in turn binds the CSL and disassembles a repression complex with coactivators MamL and p300

22
Q

NF-kB protein complex activities

A

Involved in cellular responses to stress, cytokines, free radicals, UV irradiation, oxidized LDL and bacterial/viral antigens

23
Q

T/F. NF-kB is only found in B cells.

A

False, it is found in almost all animal cell types.

24
Q

NF-kB structure

A

5 subunits : p50, p52, p65, c-Rel and RelB, which can homo and heterodimerize

25
Q

NF-kB disregulation can be found in these diseases

A

Autoimmune, cancer, sepsis and inflammation

26
Q

Inhibitor of NK-kB and target of upstream signaling cascades

A

IkB

27
Q

What structural similarity do all NF-kB family members share?

A

Rel homology domain in N-terminus

28
Q

How are NF-kB class 1 proteins synthesized and modified?

A

Synthesized as large precursors (p105/p100) and processed into shorter mature subunits (p50/p52)

29
Q

Hallmark structural feature of IkB proteins

A

Ankyrin repeat domain, important in mediating assembly with REL proteins

30
Q

How does IkB inhibit RelA nuclear localization?

A

By masking the nuclear localization signal, preventing RELA from localizing or binding DNA

31
Q

What triggers degradation of IkB?

A

Phosphorylation of tandem serine residues at N-terminues, triggers polyubiquitylation and proteasome-mediated degradation

32
Q

NFkB simplified pathway (4 steps)

A
  1. Signal binds receptor
  2. Receptor activates enzyme IkB kinase (IkK), which phosphorylates IkB inhibitor
  3. Phosphorylation targets IkB for degradation, and RelA/p50 localize to nucleus.
  4. RelA/p50 bound by coactivator and RNA pol to affect gene transcription by binding to response elements (REs)
33
Q

T/F. Types of NF-kB dimers determine downstream gene regulation

A

True, c-Rel/p50 heterodimer recognizes different REs then a p50 homodimer

34
Q

Microscopy techniques to study nuclear signaling pathways (3 examples)

A

FRET to detect dimerization, fluorescence microscopy to follow protein localization after inhibiting pathways, TIRF and single molecule imaging

35
Q

TNF pathway (5 steps)

A
  1. TNF receptor occupied by TNF recruits adapters TRADD and TRAF
  2. TRAF2 is an E3 ubiquitin ligase that associates with E2 complex, ubiquitination is important for scaffolding
  3. Receptor complex attracts TAK1 and other additional components.
  4. TAK1 phosphorylates and activates IKK, which disociates from NEMO (NFkB essential modifier)
  5. IKK phosphorylates IkB at 2 tandem serines, then IkB is degraded, liberating NF-kB heterodimer p50/p65
36
Q

WNT signaling pathway roles

A

Embryonic development, carcinogenesis role, growth stimulation

37
Q

B-catenin role in Wnt signaling?

A

B-catenin sequestered by GSK3/APC complex, but is freed by proteolysis following WNT binding to Frizzled receptor

38
Q

Two cell-surface proteins which Wnt binds together to initiate signaling

A

Cysteine rich domain of Frizzled (Fz) receptor, and Fz co-receptor LRP5/6

39
Q

Wnt signaling pathway basic steps (3)

A
  1. Wnt binds Fz + LRP5/6
  2. LRP5/6 phosphorylated by CKI-gamma, makes binding sites for attachment of scaffolding protein Axin. DSH also binds.
  3. DSK3 now inhibited, stabilizing B-catenin and allowing it to accumulate in cytoplasm, where it then enters nucleus to activate transcription
40
Q

Shh (hedgehog signaling) basic steps

A
  1. Hedehog inhibits Patched (Ptc), which in turn ceases to inhibit Smo
  2. Smo adapter can then be phosphorylated/activated through variety of kinases - PKA, CkI, Gprk2
  3. This converts Ci into CiA, which then translocates to nucleus and affects gene expression (in another slide, says instead Gli1/2 is released from its latent form and then translocated into the nucleus)
41
Q

What does graded signaling mean?

A

Different protein concentrations induce different subsets of genes, gene activation occurs at thresholds. For hedgehog (Hh), if you have diff concentrations of Hh, you get diff levels of intracellular signaling

42
Q

3 types of ligands

A
  1. lipophilic, can pass through membrane without assistance
  2. Soluble, requires ion channels, GPCRs, etc
    3.
43
Q

4 types of ligands

A
  1. lipophilic, can pass through membrane without assistance
  2. Soluble, requires ion channels, GPCRs, etc
  3. Matrix associated
  4. Membrane bound
44
Q

Membrane bound receptors which produce second messenger when stimulated (4)

A

GPCRs, enzyme-linked receptors, cell-matrix adhesion receptor, cell adhesion molecules

45
Q

Ran-GTP

A

Involved in nuclear import/export

P&R (15 decks)

Brainscape helps you reach your goals faster, through stronger study habits.
© 2024 Bold Learning Solutions. Terms and Conditions