Regulation by "factors"

Cells fail to divide if an essential nutrient is left out.  Essential nutrients include growth factors (GF) or nutritional factors (NF).  For esample  fibroblasts require a platelet derived GF - PDGF for short.  Platelets fragment and release PDGF at the site of injury causing the rapid division of fibroblasts that helps heal the wound.

Q:What are "fibroblasts"?
A:They are the main cells of connective tissue having receptors for PDGF on their membranes

Regulation by cell density

Normal cells form one layer and stop dividing because a crowd of cells competes for nutrients and minute quantities of growth regulators.  This is process by which crowding prevents cell division is called density-dependent inhibition.  To divide, most cells require adhesion to a substratum (ie. inside of culture jar or ECM of a tissue).  Cancerous cells are an exception.

G₁ Phase as a Part of Regulation

At the end of this phase - just before S Phase - it is GO! or NO GO! for mitosis.  This crucial time is called the restriction point.  If internal and external cues are favorable, its GO!  If its GO!, the cell proceeds to S Phase to replicate its DNA in preparation for mitosis/meiosis.  If NO GO!, the cell exits the cycle and goes into a nondividing state called G₀ Phase (most human cells are in this phase).  The most specialized cells (neurons and muscle) will not divide again, but some cells (i.e., liver) can be "called back" into the cycle by certain environmental stimuli (i.e., GF released after an injury)

Regulation by Cytoplasmic Volume

A cell must grow to a certain size during the first G Phase before S Phase in order to proceed

Q:How does it work?
A:Cytoplasmic volume is constantly increasing while the genome size is remaining constant; without some regulation mechanism, imagine daughter cells getting smaller and smaller with each cycle.

Regulation by Cyclical Changes:  The Mitotic Clock

Rhythmic fluctuations in regulatory protein concentrations are called a clock.  Some of these proteins are protein kinases (enzymes that control activities of other proteins).  By adding Phosphate to the target protein, the protein kinase turns the target protein on (usually).  A protein kinase only active when bound to a particular cyclin = a Cyclin-dependent Kinase (CdK). CdKs are in uniform concentration but activity rises and falls with the concentration of its cyclin adapter.

MPF (maturation promoting factor):  a specific CdK-cyclin

1. cyclin accumulates in 2nd G Phase
2. associates with the protein kinases
3. prophase initiated activating diverse proteins of mitosis
4. near the end, MPF activates a protein that destroys cyclin.  The other half, CdK, persists in its inactive form until associating with new cyclin formed during interphase.
   (examples: phosphorylation of certain chromatin proteins causes chromosomes to condense during prophase and the nuclear membrane disperses in prometaphase directly or indirectly when proteins in the lamina are phosphorylated)
5. fluctuating cyclin-CdK complexes TIME OTHER STAGES (ie certain c-CdK complex is required to pass the restriction point)

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Next:  "Cancer."