Tissue Homeostasis

Proliferation

Cell reproduction through mitotic cell division

Interphase

• Not part of cell division

• G1: replicate cell organelles

• S1: replicate DNA

• G2: period of cell growth (enzyme & protein synthesis)

Cyclin & Cyclin-Dependent Kinases (CDK)

• CDKs is the enzyme

• Cyclins is the regulatory proteins

• CDKs binds to cyclin to form active complex that drives cell cycle

• Cycling proteins is the concentration of different cyclin proteins rises and falls throughout cell cycles

Cell-Cycle Regulatory Proteins

Phase	Cyclin	CDK
G1	Cyclin D1/2/3	CDK4/6
G1 → S	Cyclin E	CDK2
S	Cyclin A	CDK2
G2 → M	Cyclin A	CDK1
M	Cyclin B	CDK1

Cell Cycle Fluctuation of Cyclins

• Cyclin D synthesizes due to growth factor and stays active until the end of mitosis

• Cyclin B must be destroyed for cell to exit mitosis and cytokinesis to start

Cell Kinase Inhibitors (CKI)

Cip/Kip inhibitors (universal inhibitors)

• p21, p27, p57

INK4 inhibitors (specific for CDK4/6)

• p15, p16, p18, p19

Cell-Cycle Checkpoints

Detect malfunctions within the cycle, if defects are detected, repair are initiated or apoptosis will occur

• G1 checkpoint: checks for DNA damage

• S1 checkpoint: monitors accuracy of DNA replication

• G2 checkpoint: checks for unreplicated/damaged DNA

• M checkpoint: ensures all chromosomes aligned correctly

Epigenetis

• Gene-silencing (gene expression is off)

• Most common is methylation of cytosine nucleotides

• Happens in genes or promote regions (CpG islands)

• DNA methylation and histone acetylation/deacetylation modify to allow successive genes to be activated/deactivated

Translation Inhibition

Block protein expression by inhibiting translation or facilitating degradation of target mRNA and silence genes

• miRNA

• siRNA

Senescene

Cells that are metabolically active but can no longer divide (growth arrested)

Terminally Differentiated

Cell becomes specialized and cannot divide

Necrosis

Cells that were murdered

Apoptosis

• Programmed cell death

• Regulate number of mature cells

• Activation of apoptotic caspases (apoptosis enzyme) in platelet production and release from mature megakaryocytes, and in the final stages of erythrocytic maturation

• Increase in myelodysplastic syndrome (bone marrow disorders)

• Decrease in acute leukemia

Quiescent Phase

• G0 is a reversible, non-dividing state

• Can re-enter cell cycle when stimulated by growth factor, or injury

Aneuploidy

• The next event begins before the previous event is finished

• Leads to abnormal chromosome numbers