chapter 6

True or False: Cancer cells make relatively large modification to the control machinery inside cells

False

•Cancer cells make relatively __**minor modifications**__ to the control machinery inside cells; tweak existing controls

True of False: Single cell can express over 20,000 proteins

True

Are most of the proteins expressed in a cell involved for cell signaling?

yes

Immediate early genes

the genes that have increased expression have the proteins already in theme

When cells are exposed to growth factors after being deprived for a certain amount of time, they express certain genes right away called ______ ; this does not require new protein synthesis

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* Immediate late genes


* Delayed early genes


* Protein dependent genes


* Immediate early genes

Immediate early genes

True or False: Immediate early genes are dependent on the synthesis of new proteins

False

If **cycloheximide**, a drug that shuts down protein synthesis is added along with the fresh serum, induction of the immediate early genes proceeds normally – What does this tell us??

the genes that have increased expression, have the proteins in them already

**cycloheximide**

a drug that shuts down protein synthesis

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What’s the difference between immediate and delayed early genes?

\-**Immediate early genes** already have the transcription factors/proteins there and do NOT need to be synthesized

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\-**Delayed early genes** need newly synthesized proteins/transcription factors in order to be activated

What type of early genes are seen in the orange box?

Delayed or immediate?

Delayed early genes

* new proteins were synthesized in order to activate or express them

What type of early genes are seen in the green box?

Immediate early genes

* The cell already had preexisting transcription factors that needed to be activated in order to express the genes
* No synthesis of proteins required

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T or F: Growth factors only cause cells to grow

False

Growth Factors can induce a variety of cellular changes

What are ways growth factors can affect a cell?

**Growth Factors can…**


1. Increase the rate of protein synthesis
2. Induce motility of cells
3. Reorganization of the cytoskeleton
4. Protect cells from activation of apoptotic pathways

All of the following are potential effects of growth factors **except**


1. inhibition of apoptotic pathways
2. induction of cell motility
3. decrease in the rate of protein synthesis
4. reorganization of the cytoskeleton to promote changes in cell shape

decrease in the rate of protein synthesis

What cellular change is seen ?

Cytoskeletal changes

On the left, there’s no serum and it localized to the surface

On the right is the affected cell, you can see the adhesions, adhering to the substrate is seen

What happens after transphosphorylation ?

Following transphosphorylation, the growth factor receptor attracts cytoplasmic proteins to specific phosphotyrosines

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Why does each RTK attract its own set of downstream signaling parters?

The proteins recognize the sequence of amino acids that are next to the tyrosine

The SH2 domains of proteins bind to_____


1. phosphorylated tyrosine residues
2. acetylated lysine
3. phosphorylated lysine residues
4. phosphoserine

1. phosphorylated tyrosine residues

What do the numbers in the picture denote?

what do the letters indicate?

Numbers denote the position of the tyrosine residues in the polypeptide chain

Letters indicate the amino acids next to tyrosine (Y) that are recognized by the proteins listed via the SH2 domain

How do proteins recognize the amino acid sequence next to the tyrosine?

The SH2 Domain

Can also recognize phosphorylation tyrosine

What does SOS do in the pic?

It coverts GDP to GTP which activates Ras

What sequences are seen within the intermolecular links between RTK and Ras?

Receptor→ Grb2 → Sos→Ras Or

Receptor →Shc → Grb2 → Sos → Ras

MAPK

mitogen-activated protein kinase

Erk

extracellular signal-related kinase

Ets transcription factor

**Ets transcription factor** – stimulates expression of important growth-regulating genes, i.e. Fos, Cyclin D1, p21

What is the middle pathway?

The Ras   → Raf → MAP kinase pathway

What does the Ras → Raf → MAP kinase pathway do?

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\*\*\*__***Raf pathway is responsible for most of the transforming powers of Ras oncoproteins******__

**This pathway induces the gene expression of Fos and Jun transcription factors** – associate with one another to form AP-1 – AP-1 acts as a transcription factor and is often hyperactivated in cancer cells

this pathway **also confers anchorage independence and loss of contact inhibition**;

also **contributes to changes in cell shape associated with transformation by the** ***ras*** **oncogene**

What happens when raf protein kinase is introduced into cells in a mutant oncogenes form?

\*\*When Raf protein kinase is introduced into cells in a mutant, oncogenic form, it can **evoke most of the transformation phenotypes induced by the ras oncoprotein**; Raf pathway is responsible for most of the transforming powers of Ras oncoproteins.

What’s erk 1/2

transcription factors because they can translocate into the nucleus

Are ras proteins always anchored to membrane?

Yes

Which pathway is involved mostly in suppression of apoptosis?

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The PI3 kinase pathway

First one

PTEN

****PTEN** = phosphatase that removes the phosphate that was added by PI3K from PIP3 to deactivate this pathway

True or false: PI3K attached phosphates to proteins

False

\*\*PI3K attached phosphates to a lipid not a protein

What happens when activated Ras bonds to PI3K

\*\*When activated Ras binds to PI3K it causes it to be closely associated with the plasma membrane

What happens when AKT/PKB is activated

Akt/PKB activation also influences **angiogenesis** (The production of new blood vessels) – this is poorly understood

What does the Ral pathway control?

The cytoskeleton

Which pathway controls the cytoskeleton?

Ral pathway

Third one

Filopodia

**Filopodia** – small fingerlike extensions that the cell uses to explore its environment and form adhesions with the extracellular matrix

Lamellipodia

**Lamellipodia** – broad ruffles extending from the plasma membrane found on the leading edges of motile cells

What do sec5 and exo84 contribute to in the Ral pathway?

Sec5 and Exo84 contribute to **Ras-mediated anchorage independent growth**

What type of proteins are cdc42 and rac

Cdc42 and Rac are **Rho proteins**; GTPases (GTP-GDP bound)

What are rho proteins involved in?

Rho proteins are involved in **reconfiguring the structure of the cytoskeleton** and the attachment the cell makes with its physical surroundings; __***control cell shape and motility; in cancer cells -- invasiveness***__

What pathway is shown?

Jak-STAT pathway

Cytokines

**Cytokines =** growth factors that stimulate components of the hematopoietic system

What do STATs do

\*\*STATs activate target genes that are important for cell proliferation and cell survival; *myc,* Cyclin D1 and D3

What’s STAT 3 know for?

STAT3 known to be constitutively active in a number of human cancers including melanomas and breast cancers

Which mutant proteins can transform normal cells into cancer cells?

Mutant STAT 3

Mutant STAT 2

Mutant STAT 1

Jak 1

Tyk 2

**mutant STAT3** protein can transform normal cells into cancer cells

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Ras is active when it is bound to _______

GDP

GTP

ATP

ADP

GTP

What is the role of mTOR in the PI3K pathway?

Stimulate protein synthesis (cell growth)

All of the following are molecules that bind to receptors that activate Jak-STAT signaling pathways except

* EGF


* interleukins
* interferon

egf

Which signaling pathway is most involved in inhibiting apoptosis?

PI3K

Ral-GEFs

Raf

Jak/STAT

PI3K

In the ras-raf pathway, Ets, Elk-1, and SAP-1 represent

* transcription factors that are inhibited by Erk1/2
* transcription factors that are activated by Erk1/2
* translation initiation factors that are activated by Erk1/2
* kinases that phosphorylate other proteins in the cell

* transcription factors that are activated by Erk1/2

The expression of delayed early genes

* does not require the binding of transcription factors
* does not require new protein synthesis
* is dependent on the translation of new transcription factors
* is dependent on the presence of transcription factors being present inside the cell before it is exposed to growth factors

* is dependent on the translation of new transcription factors