MDM2: Oncogene Chan Lee. Discovery of MDM2: starting with tumor suppressor p53.

Slides:

Advertisements

Similar presentations

P53 The Master Guardian of the Genome. p53 gene mutations in human tumors Greenblatt et al. (1995) Cancer Res. 54: %

Advertisements

p53 Revealed character as a tumor suppressor gene in 1989.

P53 gene mutations in human tumors Greenblatt et al. (1995) Cancer Res. 54: %

P53 The Master Guardian. R point Cell cycle control involves several checkpoints and checkpoint (molecular breaking) mechanisms.

MDM2 inhibits p300-mediated p53 acetylation and activation by forming a ternary complex with the two protein 生科系 04 級賴保諺 Eric Kobet, Xiaoya Zeng,

P73 Shatil Amin March 27 th Content I.Structure and Function II.Regulation III.Is it involved in human cancers?

P53 gene mutations in human tumors Greenblatt et al. (1995) Cancer Res. 54: %

BRCA1 The First Breast Cancer Gene Presentation By Liz Mosley.

C22 Cancer and the Immune System Cell births ~ cell deaths; production of new cells is regulated Cells that do not respond to normal growth controls can.

P53 has a key role in integrating the cellular responses (pink boxes) to different types of stress (blue boxes). Activation of p53 can result in a number.

Malignant Melanoma and CDKN2A

Tumor genetics Minna Thullberg

Apoptosis (Programmed Cell Death). Apoptosis vs Necrosis Level of stress, change in environment stress apoptosisnecrosis.

1. p53 Structure, Function and Therapeutic Applications Provider: Dr.Davood Nourabadi(PhD,medical physiology) mdphysiology.persianblog.ir.

P53 Missense Mutation Cancer. Outline Disease related to p53 Role and regulation pathway Structure of p53 Missense mutation and consequences Experiment’s.

Chapter 18 Regulation of Gene Expression Dr. Joseph Silver.

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

Mutational analysis of 35 bladder cancer cell lines using RNA-seq.

Cancer Detection and Diagnosis Early Cancer May Not Have Any symptoms Pap Test Mammograms Blood tests Prostate-specific antigen (PSA) Carcinoembryonic.

Eukaryotic Gene Control. Gene Organization: Chromatin: Complex of DNA and Proteins Structure base on DNA packing.

Regulation of gene expression by mutant and

Cell Cycle Regulator and Tumor Development

Natasha Adlakha Bio445. Discovery in Breast Cancer Reverse Genetics BReast CAncer Gene Chromosome 13 Tumor suppressor gene Penetrance Familial,

Cellular Senescence What is it? What causes it? Why is it important (cancer and aging)?

Tumor Suppressor Gene Involved in Breast and Ovarian Cancers SCIENCE96/gene.cgi?BRCA1.

YEATS4 Is a Novel Oncogene Amplified in Non– Small Cell Lung Cancer That Regulates the p53 Pathway Speaker:Dai-Wei Hsuan Adviser:Dr. Guor-Mour, Her Data:2015/04/22.

Bmi-1 in Cancer Cancer genetics 2012/04/ 전종철

Tumor-suppressor genes Tumor-suppressor genes, function like brakes, keep cell numbers down, either by inhibiting progress through.

EUKARYOTIC CELL SIGNALING VII Abnormal Signaling in Cancer Signaling to p53 Dr. Ke Shuai Office: 9-240M Factor Tel: X69168

c-Myc A Biological Paradox

YEATS4 Is a Novel Oncogene Amplified in Non– Small Cell Lung Cancer That Regulates the p53 Pathway Speaker:Dai-Wei Hsuan Adviser:Dr. Guor-Mour, Her Data:2015/04/22.

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

Cell Cycle Checkpoints The Guardian Mechanisms of

Mouse Double Minute 2 (MDM2)

Lecture #8 Date _________

Genetics and pathology of pancreatic cancer

p53 function and regulation in normal cells and cancer cells

HCDC4 functions as part of an E3 ligase in the ubiquitin-mediated degradation of proteins. Homologues: FBW7 (H. sapiens); Archipelago (D. melanogaster);

Prolyl‐hydroxylase‐domain proteins regulate hypoxia inducible factor‐α in response to O2 availability. Prolyl‐hydroxylase‐domain proteins regulate hypoxia.

The Role of SMAD4 (DPC4) in Cancer

Cancer as a genetic disease

Regulation of the Cell Cycle & Cancer

Molecular Basis Of Cancer

The Role of Myc A Master Regulator Gone Awry

TSC1 in Facial Angiofibromas

The guardian of the genome

Lecture #8 Date _________

Extracellular Regulation of Apoptosis

BIOLOGY 12 Cancer.

Genomic alterations in breast cancer cell line MDA-MB-231.

ARF and p16: One Locus, Two Tumor Suppressors

PTEN Tumor Suppressor and Cancer

Transcriptional Addiction in Cancer

Transcription Initiation:

Volume 130, Issue 4, Pages (August 2007)

A New FOXO Pathway Required for Leukemogenesis

Tumor Metabolism: MAGE-A Proteins Help TRIM Turn Over AMPK

Alternative and aberrant splicing of MDM2 mRNA in human cancer

Canonical gliomagenesis mediators EGFR, P53, and retinoblastoma protein (RB1) are important for cancer signaling. Canonical gliomagenesis mediators EGFR,

Figure 2 Signalling downstream of the IL-6 receptor

Regulation of p53 by MDM2. p53 and MDM2 form an autoregulatory feedback loop. p53 stimulates the expression of MDM2; MDM2, in turn, inhibits p53 activity.

The TRIP from ULF to ARF Cancer Cell

EGFR and cetuximab sensitivity of SCCUAT

p53 loss affects several steps of the metastatic process.

P53 restoration in a syngeneic transplant model of Mdm2Tg p53Neo/Neo CreER angiosarcoma. p53 restoration in a syngeneic transplant model of Mdm2Tg p53Neo/Neo.

Targeting the CBP–p300 synthetic lethal axis.

Oncogenic potential of the extraribosomal functions of RPs

PTEN and p53: Who will get the upper hand?

No Driver behind the Wheel? Targeting Transcription in Cancer

Presentation transcript:

MDM2: Oncogene Chan Lee

Discovery of MDM2: starting with tumor suppressor p53

MDM2 discovery

MDM2 Discovery- Murine Double Minute Gene

MDM2 Discovery: A gene amplified in sarcoma Mdm2 Gene Amplification in Gastric Cancer Correlation with Expression of Mdm2 Protein and p53 Alterations, Thomas Günther, et, al

In a Normal Happy Cell Low p53

Under Stress – p53 activation X 1) Growth Arrest 2) Apoptosis

Why MDM2 binds to p53? Auto-regulatory Negative Feedback Loop

In Normal cell, MDM2 is a negative regulator 1) Binds to p53 transactivation domain 2) Induces nuclear export 3) Ubiquitinate for degradation

1) MDM2 inhibits by binding to p53 transactivation domain

2) MDM2 Induces Nuclear Export

3) MDM2 is a ubiquitin ligase E3 P53 is polyubiquitinated by MDM2

MDM2 degrades p53

MDM2 Mutation: knock-out is Lethal X X

MDM2 and Cancer 7 % Mdm2 amplification in 3000 tumors from 28 tumor types Osteosarcomas and soft tissue sarcomas have highest rate 20%, 16%

Nutlin Targeting the MDM2-p53 complex

Summary: MDM2 is a Oncogene