Six steps of information transfer in eukaryotes that constitute potential regulatory points of gene expression Plasma membrane DNA Primary RNA transcript mRNA Transcriptional control mRNA Interactive mRNAProtein Active/ Inactive Protein Processing transcript Nuclear envelope Transport control mRNA stability control Translational control by ribosome selection Protein posttranslation control 1 2 3 45 6 Copyright © motifolio.com5111318 Scheme of events for protein translation from a mRNA molecule Met Met Met aa aa aa aaMet 5’ mRNA 1 2 3 4 5 Initiator tRNA Small ribosomal subunit with initiation factors bound Binding of small subunit to mRNA, followed by recognition of Initiation codon Binding of large subunit to mRNA, followed by binding of second tRNA Met tRNA Next amino acyl tRNA binds Continued peptide bond formation, until termination codon is reached Release of completed polypeptide, free tRNA and ribosome subunits Release factor (protein) Met aa Copyright © motifolio.com5111315 Replication bubble Local opening of DNA helix RNA primer synthesis New DNA chain starts leading-strand synthesis RNA primers start additional New DNA chains |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||| |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||| Copyright © motifolio.com5111196 How a growth factor signals the cell cycle control system G1 checkpoint S G2 M G1 Control System Growth factor Plasma membrane Receptor protein Signaling pathway Relay proteins Copyright © motifolio.com5111186 Cell cycle checkpoints M G2 G1 S Damaged DNA Chromosome misaligment Unreplicated or Damaged DNA STOP STOP STOP Copyright © motifolio.com5111187 Copyright © motifolio.com Ion channel actions via G-protein coupled receptors Neurotransmitter Receptor G-protein G-protein-gated ion channel 5111168 Copyright © motifolio.com Enzyme actions via G-protein coupled receptors Second messengers Neurotransmitter Receptor G-protein Enzyme 5111169 Copyright © motifolio.com Na+ / K+ pump Na+ K+ Extracellular Intracellular 5111170 Activation of cAMP and gene transcription cAMP Inactive PKA Activated PKA AC Transcription Translation Inactive CREB Activated, phosphorylated CREB Nucleus Cell membrane CBP Copyright © motifolio.com5111139 Inositol phospholipid pathway Cell membrane Endoplasmic reticulum lumen IP3 PIP2 Activated Gq  subunit Activated PLC- DAG Activated PKC Ca2+ Ca2+ G-protein linked receptor Copyright © motifolio.com5111140 Cell surface receptors – G-protein linked receptors G protein Enzyme Activated G protein Enzyme Activated enzyme Copyright © motifolio.com5111121 Caspase activation by the extrinsic and intrinsic pathways Smac IAP Cyt C ATP Apaf-1 Procaspase 9 Apoptosome Procaspase 3 Caspase 3 Caspase 8 Procaspase 8 DISC FADD Fas FasL Cleavage of proteins leading to cell death Copyright © motifolio.com5111409 Phosphatidylinositol 3-kinase (PI3K)/Akt signaling pathway PP P P P P P P P RTK PI PI PI PDKAkt Akt PTEN PI3KIRS IKK NF-kB CREB GSK-3 FOXO 14-3-3 14-3-3 BAD Copyright © motifolio.com5111411 Schematic depicting the different phase of the cell cycle Interphase DNA synthesis Gap 2 Cell division Gap 1 G1 G2 M S Mitosis Go Cells cease division Copyright © motifolio.com5111400 Phosphorylation of pRb by cyclin/cyclin-dependent kinase (CDK) complexes Cyclin A Cdk2 Cyclin D Cdk4 Cyclin E Cdk2 Extracellular signals DNA synthesis E2F E2F R SG1 Restriction point Rb Rb + P P P P P Ser780 Thr373 Ser249/252 Ser807/811 Ser785 Copyright © motifolio.com5111401 Different forms of cell death Cell lysis Necrosis Apoptosis Autophagic Death Blebbing Chromatin copactation Cell and nuclear fragmentation Apoptotic bodies Autolysosome Lysosome Preautophagosomal structure Autophagic vesicle Autolysosome Copyright © motifolio.com5111406 Gene regulation by members of the nuclear receptor superfamily A. Glucocorticoid receptor Cortisol Hsp70 Hsp9 0 Inactive receptor IP Transcription activated Plasma membrane Nucleus Copyright © motifolio.com5111362 Gene regulation by members of the nuclear receptor superfamily B. Estrogen receptor Transcription activated Estrogen Receptor dimer Hsp90 Inactive receptor HAT Coactivat or Plasma membrane Nucleus HAT – histone acetyltransferase Copyright © motifolio.com5111363 Gene regulation by members of the nuclear receptor superfamily C. Thyroid receptor Transcription activated HAT Coactivat or HDAC Thyroid Plasma membrane Nucleus Absence of hormone Corepressor Thyroid hormone receptor Transcription repressed HDAC – histone deacetylase HAT – histone acetyltransferase Copyright © motifolio.com5111364 General schemes of intercellular signaling A. Paracrine signaling B. Autocrine signaling C. Juxtracrine signaling D. Endocrine signaling E. Synaptic signaling Hormones Endocrine cell Copyright © motifolio.com5111361 Events leading to chromosome replication 5’ 3’ 3’ 5’ Origin Origin Origin Origin 5’ 3’ 5’ 3’ Okazaki fragments Lagging strand Polymerase Primase Helicase Polymerase Lagging strand Copyright © motifolio.com5111304 Major events of DNA repair process in eukaryotic cells 5’ 3’ DNA damage Repair recognition complexes DNA glycosylase Nucleases Step 1 Recognition Step 2 Assembling complexes Step 3 Repair damage AGT GTGC TCAGCACG 5’ 3’ 5’ AGT GTGC TCAGCACG 5’ 3’ 5’ AGTC GTGC TCA 5’ 3’ 5’CACG Endonuclease Ligase ATCAA GACG TAGTT 5’ G A CTGG Helicase C=T AT G TAGTTGACTG 5’ 3’ 5’ ATCAACTGACG TAGTTGACTGC 5’ 3’ 5’ DNA polymerase & Ligase 3’ 3’ Dimer Copyright © motifolio.com5111305 DNA segments that can modulate transcription by binding gene regulatory proteins Upstream enhancer Downstream enhancer Core promoter Gene sequence CAAT TATA 30 bp ~ 80 bp +1 transcription Regulatory protein DNA binding site Polymerase Unmasked DNA sites Protein/protein interactions +1 +1 +1 A B Copyright © motifolio.com5111320 Scheme of the activity of a master gene Master gene regulatory protein mRNA mRNA Protein 1 Protein 3 Gene 1 Gene 2 Gene 3 Gene 4 On Off On Off No protein 2 No protein 4 Binding to DNA elements Copyright © motifolio.com5111321 Intracellular signaling molecules A. Cell-surface receptor B. Intracellular receptor Cytosol G protein P P P P + + - Intracellular signaling proteins Altered cell behavior DNA RNA Transcription Altered gene expression Altered cell behavior Cytosol Nucleus Copyright © motifolio.com5111359