Test 2: Lecture 41 Flashcards by jillian Bastidas

negative regulators of cell cycle are ___ for cancer

most common mutations

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The cell cycle is a regular pattern of ____

growth, DNA replication, and cell division.

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Cell cycle is a highly ___ and ___ process

evolutionarily conserved and extremely well-controlled process

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The main mechanisms of control of the cell cycle are ___ and ___

checkpoints and feedback

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if control mechanisms of cell cycle fail it leads to ___

cancer

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The cycle works the same way in all tissues, but the ___ and ___can vary according to context and organismal needs

duration and frequency

cells can live for days or years. most cells are not actively dividing

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Most tissue, differentiated cells, are actively being ___; some slowly, some quickly

renewed/ replaced

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___ cells produce differentiated cells according to the needs of the tissue

Progenitor

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The bone marrow produces ___ new neutrophils per day!

100 billion

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Cells cannot keep growing without dividing or their ___: ___ will get too high very quickly

volume to surface area

cell likes high SA and low volume

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Three stages of interphase

Gap 1 (G1): cell growth and normal functions

DNA synthesis (S): copies DNA

Gap 2 (G2): additional growth (chromatids
become replicated chromosomes)

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after cell completes interphase it goes through ___ and ___ only is ___

mitosis and cytokinesis

cell is large enough and the DNA is undamaged

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division of the cell cytoplasm

cytokinesis

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3 major checkpoints of cell cycle

G₁/S
• can DNA synthesis begin?

G₂/M
• has DNA synthesis been completed
correctly?

• commitment to mitosis

spindle checkpoint
• are all chromosomes attached to spindle?
• can sister chromatids separate correctly?

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what is the 1st checkpoint of cell cycle

G₁/S
• can DNA synthesis begin?

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what is the 2nd checkpoint of cell cycle?

G₂/M
• has DNA synthesis been completed
correctly?

• commitment to mitosis

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what is the 3rd checkpoint of cell cycle?

spindle checkpoint
• are all chromosomes attached to spindle?
• can sister chromatids separate correctly?

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Checkpoints are based on activation and
inactivation of ___

cyclin-dependent protein
Kinases (CDKs).

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CDKs are ___ until they are bound with ___ which activated the CDK.

cyclin-dependent protein
Kinases (CDKs)

inactive

cyclin

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CDKs are regulated on the protein level by ___ and ___

cyclin-dependent protein
Kinases (CDKs)

CDK activating kinases(CAKs)

CDK inhibiting kinases (CIKs)

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A cyclin-activated CDK has one or multiple
protein ___ target substrates

phosphorylation

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Phosphorylation usually leads to destruction of
the substrate (CKD and its cyclin) by \_\_\_\_

E3 ubiquitin ligase-mediated
degradation

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p16, p27 work by

preventing CDK and its cyclin from binding to each other

inhibits cell cycle

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Cyclins are primarily regulated on the ___ level. They are targets of transcription factors that become ___ and ___ in sequential fashion across the cell cycle

transcriptional

activated and inactivated (waves) one cyclin will lead to the activation of the next cyclin

cyclin D→ E→ A→ B

Rb-E2F

When Rb is unphosphorylated, E2F transcription factor and Rb are attached and is **inactive** Phosphorylation of Rb by CDK4/6 leads release of Rb from E2F, E2F then can attach to DND and leads to activation of transcription of proteins that carry out cell cycle progression – both structurally and regulatory (make other CDK, help with mitosis and proteins that help cell cycle)

Simplified view of role of Rb and E2F in the beginning of the cell cycle

type of pro-growth cytokine or growth factor

mitogen

External pro-division signals start with a ___ binding a surface receptor

mitogen any type of pro-growth cytokine or growth factor

Mitogen binding activates the receptor to initiate a signal transduction cascade that leads to transcription of cell cycle regulators such as \_\_\_

cyclin D. used in first steps of cell cycle cyclin D is needed to bind to CDK 4 to phosphorylate Rb to make it let go of E2F which allows E2F to bind to DNA and make more proteins that lead to further steps of cell cycle

G1 checkpoint is which CDK and what inhibits this step

cyclin D/CDK 6 cyclin D/ CDK 4 p15,p18,p16,p19 cyclin E/CDK 2 p21, p27, p57

S phase is triggered by __ and inhibited by \_\_

cyclin A/ CDK 2 p21/p27/p57

G2 is activated by ___ and inhibited by \_\_\_

cyclin A/ CKD 1 p21, p27, p57

M phase is activated by ___ and inhibited by \_\_\_

cyclin B/CDK1 p21,p27,p57

Cell cycle regulation can be simplified into the coordinated actions of three types of proteins: \_\_\_

(1) cyclins, (2) CDKs (3) inhibitors of cyclin-CDK complexes

\_\_\_\_ once activated, a cell cycle regulator activates things that activate it further

positive feedback

once activated, a cell cycle regulator activates things that de-activate it

negative feedback

restriction point of the cell cycle

GI check point all or nothing check point before this checkpoint cell needs growth factors to move forward, after this checkpoint there is enough + and - feedback to push the cell through cell cycle

The ___ point defines a critical time in late G1 after which a cell is committed to undergo DNA replication and is no longer sensitive to growth-factor signaling.

restriction (R)

After the R point, cell cycle progression can only be ___ by conditions of cellular stress, such as DNA damage or mitotic-spindle defects.

halted checkpoints have to fail to stop cell from dividing

Before the restriction point, the cell has a choice between cell division (growth) by continuing the cell cycle, and rest by going into \_\_\_\_

G0 (quiescence; not dividing indefinitely)

G0 phase

G0 (quiescence; not dividing indefinitely) not dividing or growing cell

what CDK and cyclin are needed at each arrow?

\_\_\_ is the best studied and likely the most important negative regulator of the cell cycle and cell survival.

p53

\_\_\_ is the most commonly mutated gene across all human cancers

p53

p53 is a transcription factor that is directly negatively regulated by ___ (sequesters p53 in the cytoplasm)

MDM2

p53 activates ___ as a critical negative feedback loop to prevent too much p53 buildup

MDM2

p53 concentrations ___ based on \_\_\_; never all on or all off.

fluctuate p53 activated MDM2, MDM2 inactivates p53 * *Tipping this balance can tip cells toward** * *cell division, survival, or apoptosis**

Steps of mitosis

PMAT prophase metaphase anaphase telophase cytokinesis

DNA is replicated in ___ of interphase

S-phase

Further cellular growth in preparation for cell division occurs in ___ after DNA has been replicated

G2 phase

Prophase

1st step of mitosis ## Footnote During prophase, chromosomes condense and spindle fibers form.

Metaphase

2nd step of mitosis During metaphase, chromosomes line up in the middle of the cell.

anaphase

3rd step of mitosis ## Footnote During anaphase, sister chromatids separate to opposite sides of the cell.

telophase

4th step of mitosis ## Footnote During telophase, the new nuclei form and chromosomes begin to uncoil.

Cytokinesis

division of the cytoplasm into two individual cells

6 hallmarks of cancer

Sustaining proliferative signaling is caused by mutation in \_\_\_

RAS ## Footnote G protein. It is **active** when bound to GTP and sends pro-growth signals to the nucleus **in healthy cell:** growth factors cause, GTP hydrolysis, and RAS is then inactive **cancer cells:** GTP is unable to hydrolysis. RAS stays active and cell gets continuous signal to grow and divide

Evading growth suppressors by ___ mutations

PTEN phosphatase **in health cell:** PTEN will dephosphorylates PIP3 into PIP2 and stop signals to cell to divide PIP3 activates AKT, which is a strongly pro-growth kinase that blocks expression of p27, p21 and other tumor suppressor genes. **in cancel cells:** PTEN is mutated and PIP3 remains turned on and cell gets continuous signal to grow and divide