Cell Cycle Flashcards
Cell Cycle- an overview
Involves DNA replication followed by cellular division to yield two daughter cells
what does atypical cell cycles lead to?
Uncontrolled cellular proliferation (hallmarks of Cancer)
What group of people are cancer incidences high in and low?
High- African American males
Low- American Indian females
Proliferation and death throughout organism’s life
In a growing organism, there is more proliferation than death
In an adult organism, cell proliferation and death are in balance
Most cells in an adult organism are cell-cycle arrested
Cancer represents an imbalance
Increased rate of proliferation
Decreases rate of cancer cell death
Differentiated cells in mature organs- divide or nah?
Examples: nerve cells, striated muscles, cardiomyocytes
DO NOT DIVIDE
Cells growing on demand- divide or nah?
Examples: fibroblasts for healing and stems cells for proliferation
DIVIDE
Blood Cell precursors- divide or nah? *in adults
Examples: Bone marrow, megakaryocytes, platelets, myeloid cells
DIVIDE
G0
The non-dividing phase of the cycle
-resting cells-
G0 –> G1
Exposure to mitogenic stimuli such as growth factors or metabolites allows some cells to move onto the cycle
G1
Cells are preparing for DNA replication thru growth and metabolism
S
DNA replication phase
G2
Cells activate enzymes needed for mitosis
Interphase
DNA replication takes place (S phase)
Prophase & Prometaphase
Chromosomes appear as two thin threads (the chromatids) held together by a centromere
Chromosomes begin to condense
Micro tubules are attached to centrioles on one side and to chromatids on the other
Metaphase
The chromatids migrate to the equatorial plane
Anaphase/telophase
Separation of 2 sister chromatids and cellular division (cytokinesis)
Megakaryocyte- Cell cycle
Skip late anaphase and cytokinesis
Result: polyploidy cell so it can fragment easily
Trophoblast- Cell cycle
Skips the late anaphase and cytokinesis phase
result is a polyploidy cell
Cancer Cells- cell cycle
Has uneven segregation of chromosomes
Results in uneuploid cells
Experimental approach to see how each phase of the cell cycle is regulated?
Isolate cells at each stage and use proteins to see how long each stage lasts
How does cyclin fluctuate between interphase and mitosis?
Increases linearly throughout interphase until mid mitosis, and then drops
Picked up again at next interphase
other proteins increase linearly
Which cyclins are bound to Cdk2?
Cyclin E or A
Which cyclins are bound to Cdk4 or Cdk6
Binds cyclin D
Which cyclins are bound to Cdc2
Binds cyclin B
Job of CDK
Once bound to cyclin –> phosphorylate so downstream targets which promote a specific cell cycle phase
Cyclin complex G2
Cdc2-cyclin B
CKI inhibition of Cyclins
Ie: p16, p21 p27
Binds to the cyclin-CDK complex and inactivated it
Elevated DKI can inhibit cell cycle progression
Elevated cyclins can further promote the cell cycle
Cyclin complex G1 and Inhibition
Beginning: CDK 4,6 with cyclin D
Inhibited by p16 (CKI and 16 kD)
End of G1: CDK2 with cyclin E
Inhibited by p21 and p27
Cyclin complex S and Inhibition
CDK 2 with Cyclin A
Inhibited by p27
What are the targets of Cyclin-CDK complexes?
The Rb protein is a tumor suppressor
Inhibitory, primary regulated thru transcription
Partners with nuclear factor (transcription factor) E2F
E2F pathway (normal)
E2F free of Rb is a potent activator of genes involved in DNA synthesis and S phase progression
E2F pathway (binded to Rb)
Cdk4-Cyclin D or Cdk6-Cyclin D is capable of phosphorylation get Rb
Cdk2-cyclin E further phosphorylate a Rb
Phosphorylate do Rb is unable to partner with E2F allowing E2F to bind to S phase gene promotors and activate them
How is the E2F/Rb pathway inhibited
By the CKIS- p16, p21, p27
Which cancers have D-type cyclins unregulated with a down regulation of p27?
Breast cancer, Colon cancer, Prostate cancer
*homogeneity: different levels for each –> some breast cancers will not have high D levels
Which cancers have the CKI p16 gene mutated or deleted?
Bladder
Deletion- 49%
Mutation- 6%
Pancreas
Deletion- 20%
Mutation-27%
Other cancers with mutated CKIs
T-ALL
Deletion- 57%
Mutation- 7%
Sporadic Melanoma
Deletion- 11%
Mutation- 9%
