Cell Identity Determined by types and amounts of proteins in the cell Protein identities and amounts...

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Cell Identity Determined by types and amounts of proteins in the cell Protein identities and amounts controlled by gene expression Differential gene expression
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Transcript of Cell Identity Determined by types and amounts of proteins in the cell Protein identities and amounts...

Page 1: Cell Identity Determined by types and amounts of proteins in the cell Protein identities and amounts controlled by gene expression Differential gene expression.

Cell Identity

• Determined by types and amounts of proteins in the cell

• Protein identities and amounts controlled by gene expression

• Differential gene expression leads to cell differentiation

Page 2: Cell Identity Determined by types and amounts of proteins in the cell Protein identities and amounts controlled by gene expression Differential gene expression.

Differentiation

Divide Differentiate

Stem Cells

DifferentiatingCell

Mature Tissue Cell

Page 3: Cell Identity Determined by types and amounts of proteins in the cell Protein identities and amounts controlled by gene expression Differential gene expression.

Blood Cell Differentiation

Page 4: Cell Identity Determined by types and amounts of proteins in the cell Protein identities and amounts controlled by gene expression Differential gene expression.

Regulating Gene Expression

gene

a

b

c

d

mRNA

protein

Gene Expression Controla) transcription

b) processingc) stabilizationd) translation

Page 5: Cell Identity Determined by types and amounts of proteins in the cell Protein identities and amounts controlled by gene expression Differential gene expression.

Cell Must be Signaled to Change

gene

a

b

c

d

mRNA

protein

Gene ExpressionControl

a) transcriptionb) processingc) stabilizationd) translation

Extracellular Signals

1) Growth factors

2) Hormones

3) Cell-Cell contacts

Page 6: Cell Identity Determined by types and amounts of proteins in the cell Protein identities and amounts controlled by gene expression Differential gene expression.

Types of Signaling

Page 7: Cell Identity Determined by types and amounts of proteins in the cell Protein identities and amounts controlled by gene expression Differential gene expression.

Example-Ras Signal Transduction

Zbigniew Walaszek et al, Cellscience Reviews Vol 1, No 3 2005

Page 8: Cell Identity Determined by types and amounts of proteins in the cell Protein identities and amounts controlled by gene expression Differential gene expression.

Ras Signal Transduction

Malorye AllisonNature Biotechnology 26, 509 - 517 (2008)doi:10.1038/nbt0508-509

Malorye Allison Nature Biotechnology 26, 509 - 517 (2008)doi:10.1038/nbt0508-509

Page 9: Cell Identity Determined by types and amounts of proteins in the cell Protein identities and amounts controlled by gene expression Differential gene expression.

Signal Transduction Complexity

http://upload.wikimedia.org/wikipedia/commons/thumb/2/29/Signal_transduction_v1.png/800px-Signal_transduction_v1.png

Page 10: Cell Identity Determined by types and amounts of proteins in the cell Protein identities and amounts controlled by gene expression Differential gene expression.

Cell Division

Fundamental property of living things

Incredibly complicated processCell must ensure coordination of growth, genome duplication and cell division Must not enter duplication cycle unless

resources are plentiful Must not divide before genome is completely

duplicated

Page 11: Cell Identity Determined by types and amounts of proteins in the cell Protein identities and amounts controlled by gene expression Differential gene expression.

Cell Cycle

Division process takes about 24 hours in humans

Page 12: Cell Identity Determined by types and amounts of proteins in the cell Protein identities and amounts controlled by gene expression Differential gene expression.

Signals and Transduction Drives Cell Cycle

Page 13: Cell Identity Determined by types and amounts of proteins in the cell Protein identities and amounts controlled by gene expression Differential gene expression.

Cell Cycle can be Stopped

Page 14: Cell Identity Determined by types and amounts of proteins in the cell Protein identities and amounts controlled by gene expression Differential gene expression.

Example, Tumor Suppressor p53

DNA damage causesp53 to be activated.

p53 blocks cell cycle

Page 15: Cell Identity Determined by types and amounts of proteins in the cell Protein identities and amounts controlled by gene expression Differential gene expression.

How Does Cancer Happen?

Mutations that incorrectly activate any protein in the Ras pathway can cause loss of cell cycle regulation

EGF, ErbB, Ras, Raf, Mek, Erk, Elk, Srf, Fos

But what about p53?

Page 16: Cell Identity Determined by types and amounts of proteins in the cell Protein identities and amounts controlled by gene expression Differential gene expression.

p53 is also Mutated

Over 50% of human tumors have p53 mutations

Page 17: Cell Identity Determined by types and amounts of proteins in the cell Protein identities and amounts controlled by gene expression Differential gene expression.

Multiple Events Required for Cancer

Alterations in the pathway of colon cancer are well known

Page 18: Cell Identity Determined by types and amounts of proteins in the cell Protein identities and amounts controlled by gene expression Differential gene expression.

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Bioinformatics Contributes to our Understanding