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• OVERVIEW OF THE CELL CYCLE
• INTRACELLULAR CONTROL OF THE
CELL CYCLE
• EXTRACELLULAR CONTROL OF
CELL DIVISION AND CELL GROWTH
fatimaArivera
FLOW OF DISCUSSION
1.Overview of the cell cycle
a. G1phase
b. S phase Interphase
c. G2 phase
d. Mitosis phase
* prophase, metaphase, anaphase, telophase, * cytokinesis
 Meiosis
2.Intracellular Control of the Cell Cycle
a. Positive: Cyclin- dependent kinase & Cyclins
b. Negative: Rb & p53
3. Extracellular Control of the Cell Cycle
a. Mitogens
b. Growth factors
c. Survival factors
fatimaArivera
OVERVIEW: THE KEY ROLES OF CELL
DIVISION
The ability of organisms to reproduce best distinguishes
living things from non-living matter.
The continuity of life is based upon the reproduction of
cells, or cell division.
Cell division is integral part of cell cycle.
OVERVIEW OF THE CELL CYCLE
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INTERPHASE
Interphase includes:
• G1 Phase:
• S Phase:
• G2 Phase:
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INTERPHASE: G1 PHASE
• Recovery from previous
division
• Cell doubles its organelles
• Cell grows in size
• Accumulates raw materials
for DNA synthesis (DNA
replication)
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INTERPHASE: S PHASE
• DNA replication
• Proteins associated with DNA
are synthesized
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INTERPHASE: G2 PHASE
• Between DNA replication and
onset of mitosis
• Cell synthesizes proteins
necessary for division
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CELL CYCLE: MITOSIS PHASE
Mitosis phase includes:
• Mitosis (karyokinesis)
• Nuclear division
• Daughter chromosomes
distributed to two daughter
nuclei
• Cytokinesis
• Cytoplasm division
• Results in two genetically
identical daughter cells
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CELL CYCLE: MITOSIS PHASE
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SIGNIFICANCE OF MITOSIS
• Permits growth and repair.
• In plants it retains the ability to
divide throughout the life of the
plant
• In mammals, mitosis is necessary:
• Fertilized egg becomes an
embryo
• Embryo becomes a fetus
• Allows a cut to heal or a broken
bone to mend
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MITOSIS PHASE: PROPHASE
What’s happening?
• Chromatin condenses.
• Centrosomes separate,
moving to opposite ends
of the nucleus
• The centrosomes start to
form a framework used to
separate the two sister
chromatids called the
mitotic spindle, that is
made of microtubules
• Nucleolus disappears
• Nuclear envelope
disintegrates
What the cell looks like?
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MITOSIS PHASE: PROMETAPHASE
What’s happening?
• Nuclear envelope
fragments
• Chromosomes become
more condensed
• A kinetochore is formed
at the centromere, the
point where the sister
chromatids are attached
• Microtubules attach at
the kinetochores
What the cell looks like?
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MITOSIS PHASE: METAPHASE
What’s happening?
• Chromosomes align on
an axis called the
metaphase plate
• Note: the spindle
consists of
microtubules, one
attached to each
chromosome
What the cell looks like?
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MITOSIS PHASE: ANAPHASE
What’s happening?
• Each centromere splits
making two chromatids
free
• Each chromatid moves
toward a pole
• Cell begins to elongate,
caused by microtubules
not associated with the
kinetochore
What the cell looks like?
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MITOSIS PHASE: TELOPHASE
What’s happening?
• Formation of nuclear
membrane and nucleolus
• Short and thick
chromosomes begin to
elongate to form long and
thin chromatin
• Formation of the cleavage
furrow - a shallow groove in
the cell near the old
metaphase plate
• Cytokinesis = division of the
cytoplasm
What the cell looks like?
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RESULTS OF MITOSIS
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• Two daughter nuclei
• Each with same
chromosome number as
parent cell ( 2n)
• Genetically identical to
each other and the
parent cell
MEIOSIS
• Formation of Gametes (Eggs & Sperm)
• Called Reduction- division
• Preceded by interphase which includes
chromosome replication
• Two meiotic divisions
• Meiosis I and Meiosis II
• Original cell is diploid (2n)
• Four daughter cells produced that are
haploid (n)
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SIGNIFICANCE OF MEIOSIS
• Two haploid (1n) gametes are brought together
through fertilization to form a diploid (2n) zygote
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SIGNIFICANCE OF MEIOSIS
• Meiosis must reduce the chromosome number by half
• Fertilization then restores the 2n number
from mom from dad child
meiosis reduces
genetic content
Too
much!
The
right
number!fatimaArivera
MEIOSIS I: PROPHASE I
Prophase I is further subdivided into
periods known as
•Leptotena
•Zygotena
•Pachytena
•Diplotena
•Diakinesis
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A physical exchange of
chromosome pieces
PROPHASE I
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METAPHASE I
Homologous pairs
of chromosomes
align along the
equator of the cell
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ANAPHASE I
Homologs separate and
move to opposite poles.
Sister chromatids remain
attached at their centromeres.
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TELOPHASE I
Nuclear envelopes
reassemble.
Spindle disappears.
Cytokinesis divides cell into
two.
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MEIOSIS II: PROPHASE II
Nuclear envelope
fragments.
Spindle forms.
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MEIOSIS II: METAPHASE II
Chromosomes align
along equator of cell.
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MEIOSIS II: ANAPHASE II
Sister chromatids
separate and move
to opposite poles.
Equator
Pole
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MEIOSIS II: TELOPHASE II
Nuclear envelope
assembles.
Chromosomes
decondense.
Spindle disappears.
Cytokinesis divides cell
into two.
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RESULTS OF MEIOSIS
• Four haploid cells with one
copy of each chromosome
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SUMMARY OF MEIOSIS I
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Nucleus
Spindle
fibers
Nuclear
envelope
EARLY
PROPHASE
I
LATE PROPHASE I METAPHASE I ANAPHASE I TELOPHASE I &
CYTOKINESIS
SUMMARY OF MEIOSIS II
Prophase II Metaphase II Anaphase II Telophase II 4 I
Undentical
haploid
cellsfatimaArivera
Mitosis Meiosis
Number of
divisions
1 2
Number of
daughter cells
2 4
Genetically
identical?
Yes No
Chromosome # Same as parent Half of parent
Where Somatic cells Germ cells
When Throughout life At sexual maturity
Role Growth and repair Sexual reproduction
COMPARISON OF DIVISIONS
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ANIMATION
FLOW OF DISCUSSION
1.Overview of the cell cycle
a. G1phase
b. S phase Interphase
c. G2 phase
d. Mitosis phase
* prophase, metaphase, anaphase, telophase, * cytokinesis
 Meiosis
2.Intracellular Control of the Cell Cycle
a. Positive: Cyclin- dependent kinase & Cyclins
b. Negative: Rb & p53
3. Extracellular Control of the Cell Cycle
a. Mitogens
b. Growth factors
c. Survival factors
fatimaArivera
Intracellular control of the cell
cycle
The cell cycle is controlled by
regulator molecules that either:
promote the process (positive)
stop it from progressing (negative)
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Positive: Cdks & Cyclins
 Cyclins
◦ The regulatory subunits of the protein
kinases that control the cell cycle
 Cyclin-Dependent Kinases (Cdks)
◦ The catalytic subunits of the protein
kinases
◦ Must be associated with a cyclin in order
to be activated
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Negative: Rb & p53
 Tumor suppressor genes
 Tumor suppressor gene codes for a
signaling protein in an inhibitory
pathway. If a tumor suppressor gene
mutates, the end result can be
active cell division.
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Negative: Rb & p53
◦ Retinoblastoma protein(Rb)
◦ prevents cell moving into S phase by
binding to a transcription factor
◦ When Rb is phosphorylated it cannot bind
so cell can move into S phase
◦ p53
◦ prevents damaged from dividing (by
inhibiting Rb pathway)
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Retinoblastoma protein (Rb)
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Rb halts the cell cycle by binding E2F. Rb releases its hold on E2F in
response to cell growth to advance the cell cycle.
• group of tumor-suppressor proteins
p53
 p53 protein halts cell division if it detects
damaged DNA
 options:
 stimulates repair enzymes to fix DNA
 forces cell into G0 resting stage
 keeps cell in G1 arrest
 causes apoptosis of damaged cell
 ALL cancers have to shut down p53 activity
 Cancer is essentially a failure of cell division
control
fatimaArivera
p53 is the
Cell Cycle
Enforcer
fatimaArivera
Major molecule players in the
cell cycle control
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Cyclin-dependent
kinases (Cdks)
Cyclins
Cdk-cyclin complex
P
regulatory proteinsphosphorylates cellular proteins
triggers passage through different
stages of cell cycle
Generic cell cycle checkpoints
fatimaArivera
Is environment favorable?
Is environment favorable?
Are all DNA replicated?Are all chromosomes
attached to the spindle?
G1
S
G2
M
G1 CheckpointG2 CheckpointM Checkpoint
G1
Cdk
G1
Cyclin
P
Active G1 Cdk-Cyclin
• Growth factors
• Nutritional state of cell
• Size of cell
Degraded G1 Cyclin
Mitotic
Cdk
Mitotic
Cyclin
P
Active Mitotic
Cdk-Cyclin
(MPF)
• Replication completed
• DNA integrity
APC
Chromosomes attached at
metaphase plate
Degraded Mitotic Cyclin
Control of the
Cell Cycle
FLOW OF DISCUSSION
1.Overview of the cell cycle
a. G1phase
b. S phase Interphase
c. G2 phase
d. Mitosis phase
 * prophase, metaphase, anaphase, telophase, * cytokinesis
 Meiosis
2.Intracellular Control of the Cell Cycle
a. Positive: Cyclin- dependent kinase & Cyclins
b. Negative: Rb & p53
3. Extracellular Control of the Cell Cycle
a. Mitogens
b. Growth factors
c. Survival factors
fatimaArivera
EXTRACELLULAR CONTROL OF THE CELL
DIVISION AND CELL GROWTH
• What regulates cell size and cell
number?
• Regulated by extracellular signals
 Mitogens
 stimulate cell division (PDGF)
• Growth factors
• stimulate cell growth
• Survival Factors
• inhibit apoptosis
fatimaArivera
MITOGEN:
PLATELET DERIVED GROWTH FACTOR
 PDGF is released by
platelets in at the site of
a wound
fatimaArivera
GROWTH FACTORS
fatimaArivera
• A signal
transduction
through
phosphatidyl
inositol pathway
• Kinase cascade
leads to increased
translation
• Some factors
stimulate both
growth and cell
cycle progression
`
fatimaArivera
fatimaArivera
 protein signals released by body
cells that stimulate other cells to
divide
 density-dependent inhibition
 crowded cells stop dividing
 each cell binds a bit of growth factor
 not enough activator left to trigger
division in any one cell
 anchorage dependence
 to divide cells must be attached to a
substrate
 “touch sensor” receptors
GROWTH FACTORS
NORMAL CELLS NEED BOTH MITOGENS AND
“ANCHORAGE”- TO ENTER A NEW CELL
CYCLE
NERVE GROWTH FACTORS
CAN INFLUENCE BOTH
RATE AND DIRECTION OF
GROWTH
SURVIVAL FACTOR: MYOSTATIN
• Myostatins are inhibitory factors that inhibit the proliferation of
myoblast that fuse to form skeletal muscle cells.
• Myostatin Mutants decrease apoptosis in muscle tissue
THANK YOU!
fatimaArivera

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Cell cycle

  • 1. • OVERVIEW OF THE CELL CYCLE • INTRACELLULAR CONTROL OF THE CELL CYCLE • EXTRACELLULAR CONTROL OF CELL DIVISION AND CELL GROWTH fatimaArivera
  • 2. FLOW OF DISCUSSION 1.Overview of the cell cycle a. G1phase b. S phase Interphase c. G2 phase d. Mitosis phase * prophase, metaphase, anaphase, telophase, * cytokinesis  Meiosis 2.Intracellular Control of the Cell Cycle a. Positive: Cyclin- dependent kinase & Cyclins b. Negative: Rb & p53 3. Extracellular Control of the Cell Cycle a. Mitogens b. Growth factors c. Survival factors fatimaArivera
  • 3. OVERVIEW: THE KEY ROLES OF CELL DIVISION The ability of organisms to reproduce best distinguishes living things from non-living matter. The continuity of life is based upon the reproduction of cells, or cell division. Cell division is integral part of cell cycle.
  • 4. OVERVIEW OF THE CELL CYCLE fatimaArivera
  • 5. INTERPHASE Interphase includes: • G1 Phase: • S Phase: • G2 Phase: fatimaArivera
  • 6. INTERPHASE: G1 PHASE • Recovery from previous division • Cell doubles its organelles • Cell grows in size • Accumulates raw materials for DNA synthesis (DNA replication) fatimaArivera
  • 7. INTERPHASE: S PHASE • DNA replication • Proteins associated with DNA are synthesized fatimaArivera
  • 8. INTERPHASE: G2 PHASE • Between DNA replication and onset of mitosis • Cell synthesizes proteins necessary for division fatimaArivera
  • 9. CELL CYCLE: MITOSIS PHASE Mitosis phase includes: • Mitosis (karyokinesis) • Nuclear division • Daughter chromosomes distributed to two daughter nuclei • Cytokinesis • Cytoplasm division • Results in two genetically identical daughter cells fatimaArivera
  • 10. CELL CYCLE: MITOSIS PHASE fatimaArivera
  • 11. SIGNIFICANCE OF MITOSIS • Permits growth and repair. • In plants it retains the ability to divide throughout the life of the plant • In mammals, mitosis is necessary: • Fertilized egg becomes an embryo • Embryo becomes a fetus • Allows a cut to heal or a broken bone to mend fatimaArivera
  • 12. MITOSIS PHASE: PROPHASE What’s happening? • Chromatin condenses. • Centrosomes separate, moving to opposite ends of the nucleus • The centrosomes start to form a framework used to separate the two sister chromatids called the mitotic spindle, that is made of microtubules • Nucleolus disappears • Nuclear envelope disintegrates What the cell looks like? fatimaArivera
  • 13. MITOSIS PHASE: PROMETAPHASE What’s happening? • Nuclear envelope fragments • Chromosomes become more condensed • A kinetochore is formed at the centromere, the point where the sister chromatids are attached • Microtubules attach at the kinetochores What the cell looks like? fatimaArivera
  • 14. MITOSIS PHASE: METAPHASE What’s happening? • Chromosomes align on an axis called the metaphase plate • Note: the spindle consists of microtubules, one attached to each chromosome What the cell looks like? fatimaArivera
  • 15. MITOSIS PHASE: ANAPHASE What’s happening? • Each centromere splits making two chromatids free • Each chromatid moves toward a pole • Cell begins to elongate, caused by microtubules not associated with the kinetochore What the cell looks like? fatimaArivera
  • 16. MITOSIS PHASE: TELOPHASE What’s happening? • Formation of nuclear membrane and nucleolus • Short and thick chromosomes begin to elongate to form long and thin chromatin • Formation of the cleavage furrow - a shallow groove in the cell near the old metaphase plate • Cytokinesis = division of the cytoplasm What the cell looks like? fatimaArivera
  • 17. RESULTS OF MITOSIS fatimaArivera • Two daughter nuclei • Each with same chromosome number as parent cell ( 2n) • Genetically identical to each other and the parent cell
  • 18. MEIOSIS • Formation of Gametes (Eggs & Sperm) • Called Reduction- division • Preceded by interphase which includes chromosome replication • Two meiotic divisions • Meiosis I and Meiosis II • Original cell is diploid (2n) • Four daughter cells produced that are haploid (n) fatimaArivera
  • 19. SIGNIFICANCE OF MEIOSIS • Two haploid (1n) gametes are brought together through fertilization to form a diploid (2n) zygote fatimaArivera
  • 20. SIGNIFICANCE OF MEIOSIS • Meiosis must reduce the chromosome number by half • Fertilization then restores the 2n number from mom from dad child meiosis reduces genetic content Too much! The right number!fatimaArivera
  • 21. MEIOSIS I: PROPHASE I Prophase I is further subdivided into periods known as •Leptotena •Zygotena •Pachytena •Diplotena •Diakinesis fatimaArivera
  • 22. A physical exchange of chromosome pieces PROPHASE I fatimaArivera
  • 23. METAPHASE I Homologous pairs of chromosomes align along the equator of the cell fatimaArivera
  • 24. ANAPHASE I Homologs separate and move to opposite poles. Sister chromatids remain attached at their centromeres. fatimaArivera
  • 25. TELOPHASE I Nuclear envelopes reassemble. Spindle disappears. Cytokinesis divides cell into two. fatimaArivera
  • 26. MEIOSIS II: PROPHASE II Nuclear envelope fragments. Spindle forms. fatimaArivera
  • 27. MEIOSIS II: METAPHASE II Chromosomes align along equator of cell. fatimaArivera
  • 28. MEIOSIS II: ANAPHASE II Sister chromatids separate and move to opposite poles. Equator Pole fatimaArivera
  • 29. MEIOSIS II: TELOPHASE II Nuclear envelope assembles. Chromosomes decondense. Spindle disappears. Cytokinesis divides cell into two. fatimaArivera
  • 30. RESULTS OF MEIOSIS • Four haploid cells with one copy of each chromosome fatimaArivera
  • 31. SUMMARY OF MEIOSIS I fatimaArivera Nucleus Spindle fibers Nuclear envelope EARLY PROPHASE I LATE PROPHASE I METAPHASE I ANAPHASE I TELOPHASE I & CYTOKINESIS
  • 32. SUMMARY OF MEIOSIS II Prophase II Metaphase II Anaphase II Telophase II 4 I Undentical haploid cellsfatimaArivera
  • 33. Mitosis Meiosis Number of divisions 1 2 Number of daughter cells 2 4 Genetically identical? Yes No Chromosome # Same as parent Half of parent Where Somatic cells Germ cells When Throughout life At sexual maturity Role Growth and repair Sexual reproduction COMPARISON OF DIVISIONS fatimaArivera
  • 35. FLOW OF DISCUSSION 1.Overview of the cell cycle a. G1phase b. S phase Interphase c. G2 phase d. Mitosis phase * prophase, metaphase, anaphase, telophase, * cytokinesis  Meiosis 2.Intracellular Control of the Cell Cycle a. Positive: Cyclin- dependent kinase & Cyclins b. Negative: Rb & p53 3. Extracellular Control of the Cell Cycle a. Mitogens b. Growth factors c. Survival factors fatimaArivera
  • 36. Intracellular control of the cell cycle The cell cycle is controlled by regulator molecules that either: promote the process (positive) stop it from progressing (negative) fatimaArivera
  • 37. Positive: Cdks & Cyclins  Cyclins ◦ The regulatory subunits of the protein kinases that control the cell cycle  Cyclin-Dependent Kinases (Cdks) ◦ The catalytic subunits of the protein kinases ◦ Must be associated with a cyclin in order to be activated fatimaArivera
  • 39. Negative: Rb & p53  Tumor suppressor genes  Tumor suppressor gene codes for a signaling protein in an inhibitory pathway. If a tumor suppressor gene mutates, the end result can be active cell division. fatimaArivera
  • 40. Negative: Rb & p53 ◦ Retinoblastoma protein(Rb) ◦ prevents cell moving into S phase by binding to a transcription factor ◦ When Rb is phosphorylated it cannot bind so cell can move into S phase ◦ p53 ◦ prevents damaged from dividing (by inhibiting Rb pathway) fatimaArivera
  • 41. Retinoblastoma protein (Rb) fatimaArivera Rb halts the cell cycle by binding E2F. Rb releases its hold on E2F in response to cell growth to advance the cell cycle. • group of tumor-suppressor proteins
  • 42. p53  p53 protein halts cell division if it detects damaged DNA  options:  stimulates repair enzymes to fix DNA  forces cell into G0 resting stage  keeps cell in G1 arrest  causes apoptosis of damaged cell  ALL cancers have to shut down p53 activity  Cancer is essentially a failure of cell division control fatimaArivera p53 is the Cell Cycle Enforcer
  • 44. Major molecule players in the cell cycle control fatimaArivera Cyclin-dependent kinases (Cdks) Cyclins Cdk-cyclin complex P regulatory proteinsphosphorylates cellular proteins triggers passage through different stages of cell cycle
  • 45. Generic cell cycle checkpoints fatimaArivera Is environment favorable? Is environment favorable? Are all DNA replicated?Are all chromosomes attached to the spindle?
  • 46. G1 S G2 M G1 CheckpointG2 CheckpointM Checkpoint G1 Cdk G1 Cyclin P Active G1 Cdk-Cyclin • Growth factors • Nutritional state of cell • Size of cell Degraded G1 Cyclin Mitotic Cdk Mitotic Cyclin P Active Mitotic Cdk-Cyclin (MPF) • Replication completed • DNA integrity APC Chromosomes attached at metaphase plate Degraded Mitotic Cyclin Control of the Cell Cycle
  • 47. FLOW OF DISCUSSION 1.Overview of the cell cycle a. G1phase b. S phase Interphase c. G2 phase d. Mitosis phase  * prophase, metaphase, anaphase, telophase, * cytokinesis  Meiosis 2.Intracellular Control of the Cell Cycle a. Positive: Cyclin- dependent kinase & Cyclins b. Negative: Rb & p53 3. Extracellular Control of the Cell Cycle a. Mitogens b. Growth factors c. Survival factors fatimaArivera
  • 48. EXTRACELLULAR CONTROL OF THE CELL DIVISION AND CELL GROWTH • What regulates cell size and cell number? • Regulated by extracellular signals  Mitogens  stimulate cell division (PDGF) • Growth factors • stimulate cell growth • Survival Factors • inhibit apoptosis fatimaArivera
  • 49. MITOGEN: PLATELET DERIVED GROWTH FACTOR  PDGF is released by platelets in at the site of a wound
  • 51. GROWTH FACTORS fatimaArivera • A signal transduction through phosphatidyl inositol pathway • Kinase cascade leads to increased translation • Some factors stimulate both growth and cell cycle progression
  • 54.  protein signals released by body cells that stimulate other cells to divide  density-dependent inhibition  crowded cells stop dividing  each cell binds a bit of growth factor  not enough activator left to trigger division in any one cell  anchorage dependence  to divide cells must be attached to a substrate  “touch sensor” receptors GROWTH FACTORS
  • 55. NORMAL CELLS NEED BOTH MITOGENS AND “ANCHORAGE”- TO ENTER A NEW CELL CYCLE
  • 56. NERVE GROWTH FACTORS CAN INFLUENCE BOTH RATE AND DIRECTION OF GROWTH
  • 57. SURVIVAL FACTOR: MYOSTATIN • Myostatins are inhibitory factors that inhibit the proliferation of myoblast that fuse to form skeletal muscle cells. • Myostatin Mutants decrease apoptosis in muscle tissue