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Title:

Cell cycle and differentiation

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Cell cycle and differentiation Exogenous control in multicellular organisms Proliferation Cell type-specific receptors MAPK (ERK1/2) b-catenin Differentiation – PowerPoint PPT presentation

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Title: Cell cycle and differentiation


1
Cell cycle and differentiation
  • Exogenous control in multicellular organisms
  • Proliferation
  • Cell type-specific receptors
  • MAPK (ERK1/2)
  • b-catenin
  • Differentiation
  • Cell type-specific receptors
  • MAPK/SMAD
  • Cell type-specific transcription factors

2
Cell Cycle
  • G0
  • Terminal differentiation
  • G1
  • S
  • Replication
  • G2
  • M
  • Division

Rb, p53, bHLHs
CyB/CDK1
Id
CyD/CDK4
CyA/CDK2
CyE/CDK2
3
Proliferation
  • Mitogens
  • FGF, EGF, HGF
  • DNA synthesis
  • CyD/CDK4 accumulation
  • Degradation of Rb
  • Activation of E2F
  • Cell size integration
  • GSK3 inhibits CDK4
  • GSK3 inhibits b-Catenin

4
Differentiation
  • bHLH transcription factors
  • Class A/general
  • TCF
  • Class B/Tissue specific
  • MyoD
  • Twist
  • Hairy
  • b-Catenin bHLH-HDAC deactivator
  • Inhibitor of differentiation (Id)
  • HLH, no b
  • No b no DNA binding

5
Myogenesis
  • GF-dependent commitment

6
Transcriptional cascades
  • ???AC?CREB?Pax
  • ?myf5/MyoD?myogenic program
  • ?Met?HGF sensitivity
  • ?wnt
  • FGF?MAPK?CDK4?cell proliferation
  • HGF?cMet?cell migration
  • Wnt?Fz?dsh--GSK3--b-catenin
  • ?TCF?proliferation
  • ?MyoD?differentiation

7
Regeneration
  • Satellite cells
  • Repair recapitulates development
  • HGF?cMet?MAPK?CyD
  • IGF1?PI3K--p27kip
  • Myostatin?SMAD--myoD
  • Ca2?Cn?NFAT/MEF2?myogenin

8
Proliferation-differentiation competition
  • Rb/E2F
  • Rb/E2F dimers repress S-phase proteins
  • E2F activates S-phase proteins
  • Rb/Id
  • Rb/Id dimers bind MyoD activate HDAC
  • Rb/Id activates differentiation
  • TCF/MyoD
  • TCF/b-catenin promotes cell cycle
  • MyoD/b-catenein promotes differentiation

9
Crosstalk between hypertrophy and hyperplasia
  • PI3K
  • mTOR increases protein synthesis
  • FOXO inhibition prevents apoptosis
  • GSK3 inhibition promotes cell cycle
  • Dsh
  • GSK3 inhibition promotes cell cycle
  • Fyn/RhoA promote adhesion FAK
  • PLC/Cn promote specification

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