Cell Cycle Flashcards
Pair the Cyclins with there kinases and function (Positive Regulators)
A
B1 and B2
D1-D3
Cdk1- triggers G2-M
for both A and Bs
Cdk4 and 6- phosphorylates protein pRB (retinoblastoma-a tumor suppressor) in G1
What substrates to Enzymes Cdc25A, B, and C bind
and what phases do they promote? (Positive Regulation)
Cdk1 for all
G1-S and G2-M
G2-M
G2-M also dephos Cdk1
Pair the main Negative Regulators with substrate and function
p21
p27
p16
Most cdk-cyclin complexes- induced by p53 tumor suppressor. Promotes cell cycle arrest and can help assemble active cdk complexes
Most cdk-cyclin complexes- Cell cycle arrest in response to growth suppressors like TGF-beta
Cdk4, Cdk6- Communicates with retinoblastoma protein prB in Growth regulation; altered in many human cancers**
What controls the restriction point in G1 phase?
phosphorylation of retinoblastoma (pRb) causes its release which then causes E2F to hyperphosphorylate–the cell is committed
What does E2F do?
Controls DNA synthesis and cell cycle/ involved in R point of G1
What must be removed from CdK1 in G2 to activate it, driving cell to M phase?
Threoinine by CAK
and
Phosphate by CDC25
Difference between Tumor, Neoplasm, Cancer, Metastasis
Tumors – Space occupying lesions that may or may not be neoplasms
Neoplasms – Autonomous abnormal growth with abnormal gene regulation
Cancer – Malignant neoplasm (metastasis can occur)
Metastasis – Secondary growth of cancer at another location
What are the hallmarks of Cancer
I'm a Gimp Rag Immune Destruction Metastasis Angiogenesis (new blood ves) Genome instability Infammation Reprogram E metabolism Acquire Self Sufficiency Growth Inhibitory ignored
What are RAS proteins?
Transmit signals for cell division in humans
-Oncogenes.. overexpression can lead to cancer
Classes of Oncogenic Retroviruses
What is the mechanism and Onogenic Element for Type 4: Retrovirus with an envelope
Transacting protein envelope encoded by retroviruses
Inappropriate cell signaling due to envelope/cell receptor interactions
Classes of Oncogenic Retroviruses
What is the mechanism and Onogenic Element for Type 1: Transducing Viruses
Oncogenic transduction of cellular gene
Cellular oncogene carried in retrovirus inserted
Classes of Oncogenic Retroviruses
What is the mechanism and Onogenic Element for Type 2: Non-transducing viruses
Cis-acting provirus
Cellular oncogene activated by proviral insertion/ integration with genome
Classes of Oncogenic Retroviruses
What is the mechanism and Onogenic Element for Type 3: Long latency non-transducing viruses
Trans-acting proteins encoded by retroviruses
Retroviral transactivating protein disrupting normal regulation
What can cause a Hepatocellular carcinoma?
Hepadnavirus
What does Herpesvirus cause?
Burketts lymphoma, Nospharyngeal carcinoma
hodgkin’s lymphoma
Gastic carcinoma
Castleman’s disease
one type is Epstein-barr virus (EBV)
What is Flavivirus?
Hep C– can cause Hepatocellular carcinoma
What can Papillomavirus cause?
Anogenital cancer, upper airway cancers
HPV
Skin cancers
What are the 3 main tumor suppressor genes and what do they do?
P53
- Controls cell cycle checkpoiont G1 G2,
- Lose control of checkpoint = cancer
- Very prevalent
P16INK4A (P16)
- Stops cell cycle, cells become irreversibly arrested
- Loss of control = unrestricted G1 checkpoint.
- Caused by Gene mutation, deletion, and CpG** island methylation
Rb (Retinoblastoma)
- Effects restriction point (RP), Not limited to loss of both alleles
- Gene may be inactivated, methylated, or sequestered
- Viral gene can cause sequestration
can cause cervical cancer if bound to HPV E7
In Chemotherapy, what is the purpose of Alkylating agents Intercalating agents Antimetabolites (ex. METHOTREXATE) Mitostatic agents Platinum Derivatives
- Alkylating agents – denature DNA and macromolecules
- Intercalating agents – intercalate between two bases, causing structure change and possibly breaking DNA bonds (CROSS LINK DNA)
- Antimetabolites (E.g. Methotrexate) – affect pool of purine/ pyrimidines to decrease DNA synthesis
- Mitostatic Agents – inhibit tubulins
- Platinum Derivatives – binds to DNA
What are the two players involved in targeting mito in Necrosis, and what are it’s mechanisms?
(i) Receptor-Interacting protein 1 (RIP1)
(ii) Poly [ADP-ribose] polymerase 1 (PARP-1)
1. Causes Ca2+ overload, uncoupled mitochondria, increase O2 consumption, ROS creation by activation of NADPH Oxidase
Apoptosis cells, mediators, and effectors
Liquid cells- hematopoietic (stem) cells and malignant counterparts
p53 mediator
Caspases 8*, 9, and 10 initiate
while 3**, 6, and 7 execute
In apoptosis, what do Bax and Bak do and what can inhibit their binding?
induce permeabilization by forming pores
BH3
What is Autophagy?
Self eating/recycling of a cell
(e) Biochemical Features: Caspase-independent and increased lysosomal activity
(f) Mechanisms:
(i) Autophagy related genes
(ii) Beclin-1 and LC3 which are suppressors
1. Beclin-1 sews a vesicle around the organelle it wants to “eat”
2. This then combines with a lysosome to release food for cell while elongating the nucleation complex
3. This can get out of hand which leads to total cell autophagy
Info on Mitotic Catastrophe (
• Mitotic catastrophe (lecture slides) (One of the main mech of cell death in cancer therapies!)
(a) Definition: Aberrant mitosis (stuck dividing) causing cell death, associated with cell cycle checkpoint deficiency
(b) Morphology: No change in membrane, larger cytoplasm w/ GIANT cell (cells can’t divide)
(c) Cells involved: Most dividing cells
(d) Inflammation: No
(e) Biochemical Features: Caspase independent, abnormal CDK1/Cyclin B activation
(f) Mechanisms:
(i) Defects in Cell Cycle Checkpoints
1. P53 – G2 checkpoint
2. BUB-related kinase (BUBR) – spindle checkpoint
3. Increased expression of multiple mitotic checkpoint genes (APC) spindle assembly -
(g) Hyperamplification of centrosomes – usually in subsequent cell cycle –
(h) Caspace-2activation during metaphase – delayed apoptosis
Fate of cells with Mitotic Catastrophe
1) Mitotic Death – Die without exiting mitosis
2) Delayed cell death - Proceed to G1, continue for many cycles (can be years) then die
3) Exit mitosis and undergo G1 arrest (Senescence)
What is senescence?
(a) Definition: Permanent cell arrest (reproductive death)
(b) Morphology: No change in membrane, flattening and increased granularity, distinct heterochromatic structure, looks like fried egg
(c) Cells involved: All cells
(d) Inflammation: Yes, but induced by cell itself, can induce inflammatory factors that also effects other cells (e.g. aging)
(e) Biochemical Features:
(f) Mechanisms: Two pathways via P53-P21** or P16-Rb***
