Exam 6 Flashcards
Six Stages of Mitosis
Prophase
Prometaphase
Metaphase
Anaphase
Telophase
Cytokinesis
M Phase
Consists of nuclear division and cytoplasmic division (mitosis and cytokinesis)
The cell has already enlarged with duplicated centrosomes and chromatids (Chromosomes)
Prophase
–Duplicated chromosomes are becoming condensed
–Mitotic spindle assembles as centrosomes move apart
Prometaphase
–The nuclear envelope breaks down into nuclear vesicles
–Chromosomes are attached to kinetochore microtubules
–Astral microtubules attach to the plasma membrane
Metaphase
–Chromosomes align at the equator of the spindle as the spindle poles both tug
Anaphase
–Sister chromatids are slowly pulled apart and synchronously separate
–Kinetochore microtubules get shorter and spindle poles also pull apart
Telophase
–The two sets of chromatids arrive at the spindle poles
–The nuclear envelope reassembles around the chromatids
–The contractile ring that divides the cytoplasm of the two cells starting to form
Cytokinesis
–May occur at any time depending on the cell type
–The contractile ring made of actin and myosin filaments divides the cytoplasm of the two cells
M phase
Period of the eukaryotic cell cycle during which the nucleus and cytoplasm divide to produce two daughter cells.
interphase
Long period of the cell cycle between one mitosis and the next. Includes G1 phase, S phase, and G2 phase.
S phase
Period during a eukaryotic cell cycle in which DNA is synthesized.
Start
Important transition at the end of the G1 phase of the eukaryotic cell cycle; passage through this transition commits the cell to enter the cell cycle and continue to S phase.
G1 phase
Gap 1 phase of the eukaryotic cell cycle; falls between the end of cytokinesis and the start of DNA synthesis.
G2 phase
Gap 2 phase of the eukaryotic cell cycle; falls between the end of DNA synthesis and the beginning of mitosis.
cell-cycle control system
Network of regulatory proteins that govern the orderly progression of a eukaryotic cell through the stages of cell division.
cyclin
Regulatory protein whose concentration rises and falls at specific times during the eukaryotic cell cycle; cyclins help control progression from one stage of the cell cycle to the next by binding to cyclin-dependent protein kinases (Cdks).
Cdk (cyclin-dependent protein kinase)
Enzyme that, when complexed with a regulatory cyclin protein, can trigger various events in the cell-division cycle by phosphorylating specific target proteins.
M-Cdk
Protein complex that triggers the M phase of the cell cycle; consists of an M-cyclin plus a mitotic cyclin-dependent protein kinase (Cdk).
S-Cdk
Protein complex whose activity initiates DNA replication; consists of an S-cyclin plus a cyclin-dependent protein kinase (Cdk).
Cdk inhibitor protein
Regulatory protein that blocks the assembly or activity of cyclin–Cdk complexes, delaying progression primarily through the G1 and S phases of the cell cycle.
anaphase-promoting complex (APC/C)
A protein complex that triggers the separation of sister chromatids and orchestrates the carefully timed destruction of proteins that control progress through the cell cycle; the complex catalyzes the ubiquitylation of its targets.
G1-Cdk
Protein complex whose activity drives the cell through the first gap phase of the cell cycle; consists of a G1-cyclin plus a cyclin-dependent protein kinase (Cdk).
G1-cyclin
Regulatory protein that helps drive a cell through the first gap phase of the cell cycle and toward S phase.
G1/S-Cdk
Protein complex whose activity triggers entry into S phase of the cell cycle; consists of a G1/S-cyclin plus a cyclin-dependent protein kinase (Cdk).
G1/S-cyclin
Regulatory protein that helps to launch the S phase of the cell cycle.
M-cyclin
Regulatory protein that binds to mitotic Cdk to form M-Cdk, the protein complex that triggers the M phase of the cell cycle.
S-cyclin
Regulatory protein that helps to launch the S phase of the cell cycle.
G protein
A membrane-bound GTP-binding protein involved in intracellular signaling; composed of three subunits, this intermediary is usually activated by the binding of a hormone or other ligand to a transmembrane receptor.
G-protein-coupled receptor (GPCR)
Cell-surface receptor that associates with an intracellular trimeric GTP-binding protein (G protein) after activation by an extracellular ligand. These receptors are embedded in the membrane by seven transmembrane α helices.
enzyme-coupled receptors
transmembrane proteins that act as both receptors and enzymes
receptor tyrosine kinases (RTKs)
cell surface proteins that receive signals from hormones, cytokines, and growth factors
oncogene
a mutated gene that has the potential to cause cancer
proto-oncogene
A gene involved in normal cell growth. Mutations (changes) in a proto-oncogene may cause it to become an oncogene, which can cause the growth of cancer cells.
tumor suppressor gene
directs the production of a protein that is part of the system that regulates cell division
Cancer
a disease caused by an uncontrolled division of abnormal cells in a part of the body
Metastases
the development of secondary malignant growths at a distance from a primary site of cancer
mitogen
An extracellular signal molecule that stimulates cell proliferation.
growth factor
Extracellular signal molecule that stimulates a cell to increase in size and mass. Examples include epidermal growth factor (EGF) and platelet-derived growth factor (PDGF).
survival factor
Extracellular signal molecule that must be present to suppress apoptosis.
programmed cell death
A tightly controlled form of cell suicide that allows cells that are unneeded or unwanted to be eliminated from an adult or developing organism; the major form is called apoptosis.
apoptosis
A tightly controlled form of programmed cell death that allows excess cells to be eliminated from an adult or developing organism.
caspase
One of a family of proteases that, when activated, mediates the destruction of the cell by apoptosis.
Bcl2 family
Related group of intracellular proteins that regulates apoptosis; some family members promote cell death, others inhibit it.
P53
a protein that regulates cell division and death, and is a key factor in preventing cancer
Astral microtubule
binds plasma membrane to hold centromere in place
kinetochore microtubule
physically binds to chromosomes
non-kinetochore microtubules
binds to other microtubules
Metaphase/Anaphase Checkpoint - 7
- Are sister chromatids both connected to opposite microtubules?
- Regulated by APC/C
- APC/C ubiquitylates cyclins by adding ubiquitin chains
- Cyclins are marked for degradation
- Cdks is inactivated
- Securin is ubiquitylated by complex and inactivated.
- Seperase is activate and degrades cohesin holding sister chromatids
Checkpoint process (10 steps) to get cyclins
–Mitogen is received by dimerized mitogen receptors
–Receptor tyrosine receptors (RTK) are autophosphorylated into their active state
–Adaptor proteins binds to RTK on inside of cell
–Ras-GEF binds to adaptor
–Inactive Ras protein (GDP) binds to Ras-GEF and is phosphorylated Ras (GTP) to become active
–Ras phosphorylates Raf
–REF phosphorylated MEK
–MEK phosphorylates MAPK
–MAPK phosphorylates Jun and ETS in the nucleus
–The transcription regulator for Myc can now by synthesized
What does Myc do?
Myc can now synthesize either cyclins or E2F.
Cyclins activate Cdks
Cdks phosphorylates Rb inhibitor
E2F can now be made
Simple Apoptosis Process - 8
–Caspases are involved but they are inactive.
–The initiator caspase is currently inactive
–There is a signal received that activates them
–The adaptor proteins activates the inactive caspa2e, it undergoes a confirmational change
–The active caspase binds to an inactive executioner caspase
–The inactive executioner caspase becomes active by cleavage
–The active executioner caspase begins cleaving multiple substrates by binding to proteins
–Apoptosis occurs
Death ligands – extrinsic - 7
–An immune system cell sends a death ligand signal
–This is received by a death receptor on an injured cell
–Death receptor changes confirmation
–The initiator caspase becomes activated by conformation
–Binds to executioner caspase which becomes activated
–Cleaves other proteins required for apoptosis
–APOPTOSIS
Lack of growth signals – intrinsic - 11
–Cytochrome c is part of the ETC in the intermembrane space
–An apoptotic signal is received
–Bax or Bac receives this signal and becomes activated
–BCL-2 in outer membrane prevents Bax or Bac from preventing this channel forming which prevents a healthy cell from dying.
–They form a channel which cytochrome c uses to move to the cytoplasm
–This binds to adaptor proteins in the cytoplasm
–The assemble that triskelion shape into an apoptosome. The middle is empty for now, and cytochrome c is on the ends of that shape (7 needed)
–Initiator caspases bonds with each of those seven arms (7 cytochrome c + 7 caspase)
–They bind with executioner caspases which activates them
–Executioner begins activating proteins
–APOPTOSIS
No BCL-2 - 7
–Bax and Bac becomes activated
–Cytochrome c leaves mitochondria
–Binds with adaptor
–Forms aptoposome
–Binds with initiator capsase
–Binds with executioner caspase
–CELL DEATH
p53 regulates cell cycle by repair - 9
–If there is degradation to DNA, the inhibitor Mdm2 unbinds from p53 as p53 is phosphorylated
–P21 Cdk inhibitor forms
–It binds to Cdk-cyclin and inhibits it from phosphorylating RB proteins
–Proteins for s-phase cannot be made
–DNA damage will be fixed (hopefully) while the cell cycle is arrested
–If DNA is fixed, p21 is broken down is removed from Cdk-cyclin
–Cdk-cyclin is activated so that Rb inhibitor is inactivated
–S-phase can proceed.
–This also occurs at G2 checkpoint into M-phase
p53 regulates cell death - 11
–P53 can also make a second protein when DNA cannot be fixed
–This new protein is called Puma
–Binds to BCL-2 and inhibits it
–BCL-2 inactivates
–Bax and Bac will now form a channel
–Cytochrome c leaves the mitochondria
–Binds with adaptor into apoptosome
–Binds with initiator caspase
–Binds with executioner caspase
–Cleaves proteins for degradation
–APOPTOSIS
What happens if p53 becomes mutated and cannot work?
Injured and damaged cells will not go into cell arrest and cannot attempt fixing their DNA
The altered DNA will be copied into proliferating daughter cells
Daughter cells will now contain altered and mutated DNA that will continue propagating.
The next generation of cells may have even more mutations as p53 still cannot put the cell into cell arrest for repairs.
Cancer then may occur.
——We have two copies of this gene from each of our parents———-
For deactivation to occur, we need mutations on both copies
UNLESS
The mutation is dominant
One of the alleles from the parent doesn’t work??
P53 is inhibited by mdm2 which requires in to go into proteosome degradation as needed
They both get phosphorylated to deactivate mdm2 and activate p53
Activated p53 goes into cell arrest or cell death protein formation
