regulation of cell number and cancer cells special limited edition packet tuesday, november 10,...

Regulation of Cell Number and Cancer

CellsSpecial Limited Edition Packet

Friday, April 21, 2023 1

There are intracellular and extra cellular signals that control the cell cycle and apoptosis.


Intracellular Controls

Intracellular controls may either be “negative” controls or “positive” controls. Negative controls will stop either the cell cycle or

apoptosis Positive controls will promote either the cell cycle or

apoptosis.


Cell CycleNegative Intra Cellular Controls


Negative Intracellular Control I

DNA is damaged during the S phase



p53 is activated and produces p53 protein.



p53 protein becomes a transcription factor for p21 gene.

p21 is activated.



p21 inhibitor protein is produced. This inhibitor protein is

an inhibitor of cyclin dependent kinase complexes. (CDK complexes)



p21 inhibitor protein inhibits CDK complex and stops the complex from activating E2F when it phosphorylates the Rb protein.

When E2F is inactive, the cell cycle stops.


Positive Intracellular Control

The Cell Cycle


Positive Intracellular Control I

When the damaged DNA is repaired (details to come in DNA replication packet), the previously mentioned process is reversed.


Positive Intracellular Control II

p53 becomes deactivated and reduces the amount of p53 proteins.


Positive Intracellular Control II

p21 gene is turned off/does not turn on.

CDK complex is activated/reactivated.

Cell cycle re-starts.


Positive Intracellular Control III

Additionally, independent signals from within, or outside, the cell produce a cascade of protein kinases. Initiates a

phosphorylation cascade.



Ultimately, the CDK complex is phosphorylated and becomes active.



Activated CDK complex phosphoroylates the Rb protein.

Rb protein is turned off.



E2F protein is released from the Rb protein.

E2F becomes active.



E2F becomes a transcription factor and binds on the S-phase genes.

The S-phase proceeds forward.


Positive Intracellular Controls

Apoptosis


Introduction—Apoptosis

It has been known for several years that many forms of cellular damage trigger leakage of mitochondria. Leakage of proteins from within the mitochondria.

This leakage indices the apoptotic response.


Positive Intracellular Controls—Apoptosis

Cytochrome C, when leaked from the mitochondria, binds to an apoptotic protease activating factor (Apaf) to form the cytochrome c-Apaf complex.


Positive Intracellular Controls—Apoptosis

The cytochrome c-Apaf complex activates the initiator capase. Capases are proteins

that behave as transcription factors and activate suicide genes. They activate

apoptosis.


Negative Intracellular Controls

Apoptosis


Introduction I

Once a capase becomes active, there is no way to stop apoptosis.

Therefore, mechanisms to prevent apoptosis from starting, under normal conditions, has been observed.


Negative Intracellular Controls—Apoptosis

Bcl proteins block the release of cytochrome C from the mitochondria and has the ability to bind to Apaf and prevent the activation of the capases.


Positive Extracellular Controls

The Cell Cycle


Introduction

Cell division is promoted by the action of mitogens. Polypeptide ligands released from paracrine sources

within the immediate area.

Mitogens are also called growth factors.


Mitogens

EGF (epidermal growth factor) activates RTK’s. RTK = tyrosine receptor kinase.

RTK initiates an intracellular transduction pathway described previously. CDK complex becomes phosphorylated and

becomes active…


Negative Extracellular

ControlsThe Cell Cycle


Introduction

Certain secreted proteins are known to inhibit cells from dividing. TGF-β

Transforming growth factor beta


Negative Extracellular Controls I

TGF-β activates TGF-β receptor (a type of tyrosine kinase receptor).



SMAD proteins are phosphorylated. Phosphorylation

cascade.



CDK complex becomes phosphorylated.

Rb protein is turned on.

Rb protein binds to E2F…stopping the cell cycle.


Positive Extracellular Controls I

Apoptosis


Positive Extracellular Controls I


regulation of cell number and cancer cells special limited edition packet tuesday, november 10,...

Documents

negative controls

rb protein

cascade of protein kinases

cell cycle restarts

apoptosispositive controls

factor apaf

leakage of proteins

cdk complexes