Flashcards in Cell cycle, apoptosis, and stem cells Deck (38):
Vast majority of cells are in this resting phase at any given time.
5 components of cell cycle control system
1. Retinoblastoma protein (pRb) 2. Cyclins 3. Cyclin-dependent kinases 4. CDK inhibitors (CDKI) 4. Transcription factors
Retinoblastoma protein (pRb)
Tumor suppressor protein encoded by Rb1. When hypophosphorylated inhibits cell progression, when phosphorylated it is inactivated and allows cell to continue to the transition from M to G1 phase. Very important in preventing excessive cell growth/proliferation.
Phosphorylation of pRb
Carried out by cyclins and CDKs. Becomes more and more phosphorylated throughout cell cycle and then hypophosphorylated after mitosis.
Cancer of the eye which originates in the retina. Caused by mutation in both alleles of Rb1 protein becomes inactivated. Can be inherited or through spontaneous mutation. Unknown why effects are not systemic.
Importance of appearance/disappearance of cyclins
Phosphorylation is easily reversible, but proteolysis (of cyclins) is not. Cyclin gene transcription helps regulate cell cycle control.
2 classes of regulatory molecules which control cell cycle
1. Cyclins 2. Cyclin-dependent kinases (CDKs)
Regulatory subunit. Sequential activation ensures correct timing and ordering of cell cycle events. Synthesized at specific stages of cell cycle in response to molecular signals.
Cyclin-dependent kinases (CDKs)
Catalytic subunit activated when bound to a cyclin. Constitutively expressed in cells.
Caused by hyperactivity of CDKs, seen in neoplasms
Cyclin C overexpression
Found in neurons and astrocytes in Alzheimer's disease
Abnormal Cyclin E expression
Seen in premalignancy and malignancy in lungs. Negative marker for prognosis.
Overexpression of Cyclin A
Found in tumors and cancer cell lines. Accelerates pRb phosphorylation, promotes entry into S-phase. Associated with ability of cells to grow in suspension.
Critical checkpoint (restriction point). Prior to checkpoint cell depends on external stimuli to progress. After checkpoint cell becomes independent of external mitogenic stimuli and can complete cell division cycle autonomously.
Tumor suppressor protein and transcription factor has role in G1/S and G2/M. Guards genome against attack by DNA damage.
3 functions of p53
1. Can activate DNA repair when damaged 2. Can induce growth arrest by holding cell cycle at the G1/S checkpoint (if held long enough time for DNA repair so cell can continue through cycle) 3. If damaged DNA cannot be repaired can initiate apoptosis
p53 in cancer
Protects against tumor development. One target inhibits cyclin E and cyclin A/CDK complexes to cause cell cycle arrest in G1. If mutated or missing one copy, particularly in combination with another mutation (like Ras), have high risk of developing tumors.
p53 and Ras
p53 affects transcription in one group of genes and Ras affects another group. Together synergistically regulate subset of genes known as cooperation response genes (CRGs) which are crucial mediators of tumor formation.
1. Apoptosis vs. 2. necrosis
1. Programmed cell death 2. Traumatic cell death with spillage of cell contents.
2 mechanisms controlling apoptosis
1. Intracellular signals (lack of nutrients, low oxygen, heat) 2. Extracellular signals (hormones, toxins, cytokines, growth factor withdrawl)
Cytokines in apoptosis
Pro-apoptotic cytokines control apoptosis by direct signal transduction.
Caspase activation pathway
Tumor necrosis factor (TNF) produced by macrophages and Fas ligand (transmembrane protein which binds to its receptor and induces apoptosis) activate pro-apoptotic enzymes called caspases than activate DNases and degrade intracellular proteins
2 abilities of stem cells
1. Self-renewal through mitosis (indefinitely) 2. Differentiate into specialized cell types and cen be totipotent or pluripotent
Ability to differentiate into all cell types and give rise to an entire organism (zygote is perfect example)
Potential to differentiate into any of the fetal or adult cell types but they themselves cannot give rise to an embryo or entire organism (cannot differentiate into extrafetal tissues such as placenta)
Unlike stem cells, cannot divide and reproduce themselves indefinitely
Progenitor cells that can give rise to multiple, but limited, cell lineages.
Progenitor cells that give rise to only one cell/tissue type.
3 types of stem cells
1. Embryonic 2. Adult 3. Induced pluripotent
Embryonic stem cells
Derived from inner cell mass of blastocyst in vitro prior to implantation. Can cause teratomas upon implantation into host.
Often benign encapsulated tumor consisting of tissues resembling endoderm, mesoderm, ectoderm (nails, skin, teeth, hair)
Adult stem cells
Example is the hemapoietic stem cell from bone marrow or umbilical cord. Can be purified from peripheral blood after mobilization from bone marrow through influence of colony-stimulating factor (G-CSF).
Induced pluripotent stem cells
Somatic (body cells as opposed to germ cells) which are reprogrammed to be pluripotent
2 ways to induce pluripotent stem cells
1. Inducing a forced expression of specific genes through transfection of adult somatic cell with a vector (often induces cancer) 2. Using purified proteins to transform adult cells into embryonic-like cells
Bidirectional trafficking and persistence in small numbers of allogenic cells (from another individual). Donated cells are genetically different from host.
Example of microchimerism. Female calf that is infertile due to influence of male hormones and blood components from male twin brother who shared the placents in utero
Most common human form. Between mother and fetus whereby cells from fetus travel through placenta to the mother. May estabilsh cell lineages and multiply. Maternal microchimerism can also occur but rare.