Ρύθμιση κυτταρικού κύκλου & Εισαγωγή στην κυτταρική σηματοδότηση Γιώργος Ρασιδάκης Επ. Καθηγητής Παθολογικής Ανατομικής, Ιατρική Σχολή ΕΚΠΑ Adj. Assistant.

Slides:

Advertisements

Similar presentations

Cell Cycle. Life cycle of a cell The cell cycle consists of: G1 = growth and preparation of the chromosomes for replication S = synthesis of DNA (and.

Advertisements

Cancer and the Cell Cycle : An overview Ken Wu. Disclaimer This tutorial is a simple and conceptual guide to the cancer module and the cell cycle If there.

THE BIOLOGY OF CANCER A group of diseases identified by uncontrolled cell growth and proliferation VirusesGenetic make-upImmune statusRadiationCarcinogens.

Alterations in the Cell Cycle and Gene Mutations that Cause Cancer

RAS PI3’K AKT RAL-GEF U0126 PD98059 PD (CI-1040) proliferation survival proliferation / differentiation survival migration proliferation RAF MEK.

Biology of cultured cells conti- Part 4 By : Saib al owini.

Cell Cycle I Molecular Cell Biology November 6, 2014 Stephen Oh, M.D., Ph.D. Assistant Professor Division of Hematology.

Cell and Molecular Biology Behrouz Mahmoudi Cell cycle 1.

Lecture 11: Signalling for Life/Death 1)Describe the eukaryotic cell cycle and the purpose of checkpoints. 2)Describe the role of cyclins and cyclin-dependent.

Lecture 17 Regulation of the Cell Cycle and Cell Death.

Cancer and the Cell Cycle

BioSci 145A lecture 18 page 1 © copyright Bruce Blumberg All rights reserved BioSci 145A Lecture 18 - Oncogenes and Cancer Topics we will cover today.

The Cell Cycle.

Chapter 23 – Cancer Genetics. Tumor Mass of abnormally dividing cells –Normal cells exhibit contact inhibition in culture Benign –Usually well-defined.

Cell Cycle Control System Checkpoints stop the cycle until go-ahead signal is received. – There are 3 checkpoints (G 1, G 2, & M) that must be passed before.

1 hr hr 8 hr 4-6 hr (M) Spindle-assembly checkpoint - confirms that all the chromosomes are properly attached to the spindles. Resting phase (G0)

The Cell Cycle Molecular Biology II. The Life Cycle of Cells The Cell Cycle Follows a Regular Timing Mechanism. Newly born cells grow and perform their.

The Cell Cycle & Cancer Mader Chapter 24.1.

Benign tumor: abnormal proliferation of cells that remain Contained and don’t spread to other tissues (ex. Skin wart) Malignant tumor: cells are capable.

Cancer as a genetic chapter 21 pp & lecture notes.

Cancer and the Cell Cycle. Outline of the lecture n What is cancer? n Review of the cell cycle and regulation of cell growth n Which types of genes when.

CDCA7 A case study in cellular regulation

Javad Jamshidi Fasa University of Medical Sciences The Eukaryotic Cell Cycle.

Genetics of Cancer Genetic Mutations that Lead to Uncontrolled Cell Growth.

G 1 and S Phases of the Cell Cycle SIGMA-ALDRICH.

Cell Cycle Stages cells pass through from 1 cell division to the next.

Chapter 12: The Cell Cycle

AH Biology: Unit 1 Control of the Cell Cycle. The cell cycle: summary G1G1 G2G2 S Interphase M Cytokinesis Mitosis.

Specialized signaling pathways 1: RTK associated pathways

Genetics of Cancer Genetic Mutations that Lead to Uncontrolled Cell Growth.

Figure 8.1 The Biology of Cancer (© Garland Science 2007)

The Cell Cycle CELL.

Lecture 10: Cell cycle Dr. Mamoun Ahram Faculty of Medicine

Cell Cycle Checkpoint.

Cell Biology Lec.5 Dr:Buthaina Al-Sabawi Date: Cell Biology Lec.5 Dr:Buthaina Al-Sabawi Date: The Cell Cycle The cell cycle, is the.

DNA Replication ORC anneals to origin ORC recruits MCM MCM recruits Cdc45p Cdc45p recruits pol  /primase complex RFC displaces pol  and recruits PCNA.

The Cell Cycle and Cancer. How is growth controlled? How is the Cell Cycle Regulated? Clue: cytoplasmic chemicals can signal mitosis.

1 Lecture 11: Signal transduction and cell cycle regulation Textbook of Receptor Pharmacology, 3rd edition.

Cell cycle – Core mechanism CDK+Cyclin APC & SCF E3 UB ligases.

Flow cytometry - FACS. Cell Cycle (reminder) Life is made of cells Cells come from cells Life/Cells reproduce.

1 The Cell Cycle “Mitosis” Packet #33 Chapter #13 Friday, November 18, 2016.

Cell Growth & Division Control of Cell Cycle | Disruptions to Cell Cycle.

Chapter 9 Cell Cycle and Cancer. Figure 17-1 Molecular Biology of the Cell (© Garland Science 2008) Cell Cycle.

CELL DIVISION CYCLE MITOSIS G1 M G2 S.

The Biology of Cancer Chapter 8: pRb and Control of the

Lung Cancer Tumour Markers

Cell cycle 김다은 성균관대학교 / 약학과

p53 function and regulation in normal cells and cancer cells

The Genetic Basis of Cancer

Alterations in the Cell Cycle and Gene Mutations that Cause Cancer

Overview of the Control of the Cell Cycle

Chap. 19 Problem 1 Passage through the cell cycle is unidirectional and irreversible due to the degradation of critical regulators by proteasome complexes.

Cells Alive – Cell Cycle

B lymphocytes produce antibodies.

Figure 1 Classical and non-classical models of the cell cycle in RB1-proficient cells Figure 1 | Classical and non-classical models of the cell cycle in.

The Cell Cycle and Understanding Cancer

Dan Gordon Gastroenterology Volume 114, Issue 4, (April 1998)

Cyclins and Cell Cycle Regulation

Cancer and the Cell Cycle

The cell cycle: The continuity of life depends on cells growing, replicating their genetic material, and then dividing. The cell cycle consists of two.

Cell Division, Cell Cycle Control, and Cancer

Size Control in Animal Development

Erratum: Knowing when to grow: signals regulating bud dormancy

Control of the Cell Cycle

Phases of the Cell Cycle

Phases of the Cell Cycle

Presentation transcript:

Ρύθμιση κυτταρικού κύκλου & Εισαγωγή στην κυτταρική σηματοδότηση Γιώργος Ρασιδάκης Επ. Καθηγητής Παθολογικής Ανατομικής, Ιατρική Σχολή ΕΚΠΑ Adj. Assistant Professor, M.D. Anderson Cancer Center (USA)

Interphase (12-24h, RNA and protein synthesis, cell growth) Gap 0 (G0) cell quit dividing temporarily or more permanently Gap 1 (G1) RNA and protein synthesis; G1 checkpoint S (synthesis) DNA replication Gap 2 (G2) protein synthesis and cell growth; G2 checkpoint Mitosis or M Phase (1-2h) division into two similar daughter cells; metaphase checkpoint Cell Cycle and Division

G1 G2 S Cell grows Cell division M DNA replication Cell prepares to divide C C C Metaphase checkpoint G1 checkpoint G2 checkpoint G0 Cells are responsive To mitogenic signals R

G2 S Cell grows Cell division M DNA replication Cell prepares to divide C C C Cyclin D1/2/3 Cdk4/6 RbE2F InactiveInactive P Rb P E2F Active S Phase Genes E2F DP Cyclin E Cdk2 Cyclin A Cdc2 Cyclin A Cdc2 Cyclin B INK4 p15,p16 p18,p19 INK4 p15,p16 p18,p19 CIP/KIP p21, p27 p57 CIP/KIP p21, p27 p57 G1

Hypermethylation of INK4 Genes in Cancer

Lymphomas “Low grade”“High grade” proliferation apoptosis (e.g. CLL/SLL, FL gr.1)(e.g. DLBCL, BL)

Burkitt Lymphoma

c-MYC promotes G1–S progression through gene activation and repression Gene activation Gene repression p15 p21 p27

Retinoblastoma

Inactivation of retinoblastoma protein

Loss of heterozygosity of Rb locus (13q14)

Advantages of ubiquitin-regulated proteolysis

Important inhibitor of cell cycle progression Haplo-insufficient tumor suppressor gene Rarely mutated or silenced in cancers p27 expression is inversely related to proliferation in many tumor types Low p27 levels due to protein degradation are associated with tumor aggressiveness and poor prognosis in cancer p27 Kip1

p27 Kip1 Regulation Post-translational regulation Phosphorylation at T187 / T157 / S10 Degradation through the ubiquitin / proteasome pathway (Cks1/Skp2) Cul1 Cyclin E Cdk2 p27 Cyclin E Cdk2 P Cyclin E Cdk2 P Cyclin E Cdk2 Ub Ub Ub Skp2 Ubc3 Skp1 Cks1 p27 degradation

p27 Kip1 Cdk-bindingsite P-richCdk-bindingsiteJAB1-bindingsite CN NLS Cyclin-bindingsite(25-51)Cdk-bindingsite(60-79) 97 S10 KISkinaseInteractingstathmin T157 Impairsnuclearimport PKB/Akt Phosphorylationsites: T187 Cdk2 DegradationUb./Proteasomepathway Stability In G1

198 JAB1-bindingsite p27 Kip1 Cdk-bindingsite P-richCdk-bindingsite CN Cyclin-bindingsite(25-51)Cdk-bindingsite(60-79) 97 S10 KISkinaseInteractingstathmin Phosphorylationsites: T187 Cdk2 DegradationUb./Proteasomepathway Stability In G1 169 T157 Impairsnuclearimport PKB/Akt 151NLS

Cyclin D Cdk4/6 Cyclin E Cdk2 CytoplasmNucleus Akt DNA Cyclin E Cdk2 E2F Cell cycle progression STOP Akt activating kinases Akt Cyclin A Cdk 2 Akt Activation Induces Cell Cycle Progression Through p27 Kip1 Downregulation

Figure 8.16a The Biology of Cancer (© Garland Science 2007)

Figure 8.16b The Biology of Cancer (© Garland Science 2007)

Σηματοδοτική οδός JAK / STAT

James E. Darnell, Jr., The Rockefeller University

Σηματοδοτική οδός PI3K / AKT / mTOR

Corradetti and Guan, Oncogene, 2006 Negative feedback loop mTOR-Rictor Activates AKT/PKB

Hay and Sonenberg, Genes Dev mTOR Controls Translation Through Phosphorylation of p70S6K and 4E-BP1 mTOR

Hay and Sonenberg, Genes Dev E-BP1 Ribosome recruitment to mRNA (5’ end) eIF-4E binds the 5’ cap structure of mRNA 4E-BP1 PPPP

Σηματοδοτική οδός RAS / MEK / ERK

Figure 6.12a The Biology of Cancer (© Garland Science 2007)

Figure 6.14 The Biology of Cancer (© Garland Science 2007)

Figure 6.15 The Biology of Cancer (© Garland Science 2007)

AKT PI3K MEKMDM2 p53 RAS ERK mTOR PTEN survival GF- R RAF GF Proliferation BAD

AKT PI3K MEKMDM2 p53 RAS ERK mTOR PTEN Επιβίωση GF- R NF RAF GF Πολλαπλασιασμός Μεταλλάξεις RAS 20-50% Μεταλλάξεις PIK3CA 20% BAD Μεταλλάξεις BRAF Μεταλλάξεις p53 50%

PTEN TSC1/TSC2 Rheb AKT PI3K PDK1 PIP3 p70S6K4E-BP1 eIF4ErpS6 GβL mTOR RAPTOR GβL mTOR RICTOR Protein translation Flt3 GRB2 RAS ERK1/2 RAF1 MEK1/2 SHC SHIP SHP GAB2 GRB2 Cyclins (e.g. D1-3, A) CDK Inhibitors (e.g. p21, p27) JAK SHP1 SOCS SHP2 STAT3 Oncogenic kinases STAT3 Transcription

Σηματοδοτική οδός NFkB

Figure 6.29a The Biology of Cancer (© Garland Science 2007)

Thank you