Cell Bio Cell Cycle, Apoptosis Flashcards
M - mitosis
nuclear & cell division (cytokinesis) - relatively short in time compared to interphase
G1: gap 1
Hours to days or more (some are so long that they may not go back into cycle)
G0: quiescent
apparently non-dividing cells - long term temporary or permanent (extended G1)
S: synthesis of DNA
remember, most cells will wind up with shortened telomeres (need nutrients, growth factors, etc.)
G2: gap 2
completion of G1 replication and replicated genome ready to undergo mitosis
interphase
- metabolically active with euchromatin & heterochromatin observed
- G1 –> G2 (no mitosis)
gap
- named because of the apparent gap in activity under the microscope
- seems like this but actually replicating and actively metabolizing (intracellular)
- G1, G0, and G2 are still metabolically, and biochemically active, etc.
- G1 variation on a theme (become longer or shorter)
- permanent G0 (cells with extended G1 phase) - post-mitotic and will not reenter the cell cycle
cell replication
central to wound healing, normal cell replacement, tumor growth (via cell cycle)
Step 1 of M phase
prophase (chromosome condense) - daughter chromosomes attached and mitotic spindle formation
step 2 of M phase
prometaphase (nuclear membrane breakdown) - dissolution begins
step 3 of M phase
. metaphase (chromosomes align) - daughter chromosomes align at metaphase plate (equator of spherical cell) and attach to MT structure (depolymerization of MT to drive separation)
step 4 of M phase
anaphase (chromosome separate) - pull at poles
step 5 of M phase
telophase (nuclear membrane reforms) - cleavage furrow forms with microfilaments
*complete chromosome separation –> reformation of nuclear membrane –> 2 daughter cells
cytoskeletal proteins in M Phase Sub-Steps
- intermediate filament depolymerization (phosphorylation) throughout cell and repolymerization (dephosphorization) in daughter cells
- nuclear lamins under nuclear membrane need to depolymerize (IF)
- microtubule depolymerization to pull spindles
- microfilament polymerization for cleavage furrow to separate cells (contractile ring)
permanently stopped cells
*post-mitotic
- “terminally differentiated” - maturation/specialization over
- upper layers of epidermis, many neuronal cells, skeletal muscle, RBC
- RBCs as characteristic terminally differentiated because they do not have a nucleus
*never enter the cell cycle
indefinitely stopped cells
- quiescent = G0 Gzero extended but can be stimulated again
- liver cells (liver damage/tissue loss would stimulate)
- some WBC (right stimulus would start cell cycle again in lab conditions)
- some can be triggered to divide with the right signal
(t/f) WBCs can start cell cycle in normal conditions
false; need to right stimulus mostly via lab conditions (most WBC are in G0)
routinely stop & go cells
- certain epidermal (lower level mitosis but never upper layers) - every 28 days
- gut lining epithelial cells (highly active and continual replacement)
- bone marrow (blood cell progenitors)
myeloid stem cell
- the ability to enter the cell cycle always
- myeloblasts have shorter-term ability to enter the cell cycle
- RBCs and platelets (no DNA/nucleus) do not go into the cell cycle
- granulocytes are mostly post-mitotic
cell cycle control
*some of the signals (dozens of + and - signals)
- external signals –> internal signals –> consequences
external positive signal (just one of many examples)
- EGF - epidermal growth factor (protein promotes skin cell replication)
- outside cell –> inside response
- many non-skin tissues produce & respond to EGF (stimulate cycling of cells)
- kidney, salivary gland, prostate, thyroid, bone marrow, lung, breast, uterus, & colon
- large precursor protein processed to small active peptide
- increased production in many cancer cells
*breast cancer treatment targeting balance (over-stimulation of EGF)
EGF receptor
*transmits a signal across the membrane
- transmembrane glycoprotein with 3 sub-regions
- one projects from the cell surface & binds EGF (extracellular)
- one span across lipid bilayer
- one projects into cytoplasm & has kinase activity (cytoplasmic portion activation) - attaches -PO4 groups to tyrosine in itself & other proteins
- kinase domain hyperactive from mutations present in cancers (excess cell growth)
- enzymatic activity built-in
external positive signals ex. EGF to internal consequences
- ligand binding & dimer formation (2 receptors) - EGF binds extracellularly
- activation of receptor kinase & self-phosphorylation at cytoplasmic tail (self and trans)
- cytoplasmic proteins associated w/ receptor are phosphorylated
- intracellular kinase activated & phosphorylate other cytoplasmic proteins (signal cascade)
- move to nucleus & cause transcription of genes encoding cell cycle promoting proteins cyclins & Cdk’s once phosphorylated
- multiple proteins activated due to increase levels of cyclin/Cdk activity
