MYC, Metabolism and Cancer

Slides:



Advertisements
Similar presentations
Control of mitochondrial gene expression Nuclear encoded mitochondrial gene expression Mitochondrial encoded genes Must be coordinated All of the enzymes.
Advertisements

CHAPTER 8 Metabolic Respiration Overview of Regulation Most genes encode proteins, and most proteins are enzymes. The expression of such a gene can be.
Cells: Metabolism and Protein Synthesis. Mitochondria: Cell Power Energy => Work O2 required to completely capture food energy into ATP Small amounts.
More regulating gene expression. Fig 16.1 Gene Expression is controlled at all of these steps: DNA packaging Transcription RNA processing and transport.
Cell: Structure and Function Transcription and Translation Nestor T. Hilvano, M.D., M.P.H.
1 Gene regulation in Prokaryotes Bacteria were models for working out the basic mechanisms, but eukaryotes are different. Some genes are constitutive,
1 Gene Regulation Organisms have lots of genetic information, but they don’t necessarily want to use all of it (or use it fully) at one particular time.
Cytoskeleton Ribosome Protein folding mRNA processing Lipid transport Transcription Cell growth Cytoskeleton Carbohydrate metabolism Protein catabolism.
Glycolysis Regualtion
Specialized signaling pathways 1: RTK associated pathways
Metabolic Syndrome: Focused on AMPK as Molecular Target for Metabolic Syndrome Bayu Lestari.
Biological organization 1. Biological molecules 2. Cellular organization.
Mitochondrial Retrograde Signaling Mediated by UCP2 Inhibits Cancer Cell Proliferation and Tumorigenesis 석사 1 학기 Tran Phuong Thao.
Regulation of glucose levels in the blood is very important Normal Fasting (Serum) ~ 70 – 100 mg/dl Elevated = Diabetes Low = Hypoglycemia Insulin from.
Cellular Respiration Cell Respiration Step 1 :Krebs Cycle
Cellular Metabolism Chapter 4.
Transcription(I) 王之仰.
Tia R. Tidwell 1, 2 ;Kjetil S#cod#x000F8;reide 2, 3, 4 ;Hanne R
Genome-wide Responses to Mitochondrial Dysfunction
The Functions of the Organelles in an Animal Cell
R. Tidwell Tia 1, 2 ;S#cod#x000F8;reide Kjetil 2, 3, 4 ;R
Metabolic functions of biotin
Sustaining Proliferative Signaling and Evading Growth Suppressors
How Cells Obtain Energy from Food
Figure 21.1 Humans can use a variable fuel input to meet a variable metabolic demand. Textbook of Biochemistry with Clinical Correlations, 7e edited by.
Cell Cycle and Protein Synthesis
Figure 2 Candidate signalling pathways of irisin in myocytess
AMPK is activated by HCMV; inhibition of the kinase blocks the glycolytic activation that is normally induced by infection and markedly reduces the production.
Cell to Cell Communication via Enzyme Linked Receptors
Figure 1 mTOR pathway activation
Nat. Rev. Nephrol. doi: /nrneph
Figure 1 A schematic representation of the HER2 signalling pathway
Nat. Rev. Endocrinol. doi: /nrendo
Figure 3 Physiological regulation of autophagy in the heart
Figure 1 mTOR complex biology
The pathway signalling starts with the binding of insulin or growth factors to insulin receptors. The pathway signalling starts with the binding of insulin.
Maria M. Mihaylova, David M. Sabatini, Ömer H. Yilmaz  Cell Stem Cell 
Identification of TOR Signaling Complexes
Unit III Information Essential to Life Processes
Patrick S. Ward, Craig B. Thompson  Cancer Cell 
A, diagram depicting receptor signaling and nutrient import.
Adiponectin, Leptin, and Fatty Acids in the Maintenance of Metabolic Homeostasis through Adipose Tissue Crosstalk  Jennifer H. Stern, Joseph M. Rutkowski,
Ageing as a Risk Factor for Disease
Inhibition of mammalian target of rapamycin: Two goals with one shot?
Metabolic Regulation of the Immune Humoral Response
mTORC1 signalling links cellular growth with autophagy
An Emerging Role of mTOR in Lipid Biosynthesis
mTORC1 Signaling: A Double-Edged Sword in Diabetic β Cells
Russell G. Jones, Edward J. Pearce  Immunity 
Mitochondria in the Regulation of Innate and Adaptive Immunity
Cancer’s Fuel Choice: New Flavors for a Picky Eater
Cancer’s Fuel Choice: New Flavors for a Picky Eater
AKT/PKB Signaling: Navigating the Network
Conserved Metabolic Regulatory Functions of Sirtuins
Figure 1 The mTOR signalling pathway
Pierre Theurey, Jennifer Rieusset  Trends in Endocrinology & Metabolism 
Regulation of carbohydrate metabolism
Biochemical Underpinnings of Immune Cell Metabolic Phenotypes
Carbohydrate response element binding protein, ChREBP, a transcription factor coupling hepatic glucose utilization and lipid synthesis  Kosaku Uyeda,
John D. Gordan, Craig B. Thompson, M. Celeste Simon  Cancer Cell 
Toshimasa Yamauchi, Takashi Kadowaki  Cell Metabolism 
Volume 7, Issue 1, Pages (January 2008)
MYC on the Path to Cancer
mTOR and Akt Signaling in Cancer: SGK Cycles In
Carbohydrate response element binding protein, ChREBP, a transcription factor coupling hepatic glucose utilization and lipid synthesis  Kosaku Uyeda,
Volume 104, Issue 4, Pages (February 2001)
Reprogramming energy metabolism in cancer
Autophagy and the Integrated Stress Response
Connections between insulin/insulin-like growth factor 1 signaling and metabolic pathways in tumor cells. Connections between insulin/insulin-like growth.
Volume 7, Issue 1, Pages (January 2008)
Presentation transcript:

MYC, Metabolism and Cancer Molecular genetics lab Eungyoung Kim

Outline Hallmarks of cancer MYC protein MYC function Building a cell Nutrient sensing Intermediary metabolism and macromolecular synthesis Organelle biogenesis Cell cycle progression Cancer therapy and Outlook 미국자료- http://onlinelibrary.wiley.com/doi/10.3322/caac.21254/pdf

MYC protein Hallmarks of cancer

MYC protein Hallmarks of cancer

MYC MYC protein Hallmarks of cancer - c-Myc, N-Myc, L-Myc - transcription factor that dimerizes with MAX to bind DNA and regulate gene expression nuclear localization sequence, DNA-binding domain, helix–loop–helix dimerization domain, and transcriptional regulatory domain underlie this functional ability.

MYC protein Hallmarks of cancer MYC enhances transcription and translation

MYC protein Hallmarks of cancer Growth factor dependent MYC activity Growth factor independent MYC activity

MYC protein Hallmarks of cancer MYC regulation in noncancerous and cancerous cells

MYC function Hallmarks of cancer 1. Building a cell Maintenance of cell membrane potentials, homeostasis for redox control and protein synthesis, are major energy-demanding cellular processes that must be sustained for survival. in the case of resting memory T cells 1) a major source of energy for homeostasis is a futile cycle of oxidation of de novo–synthesized lipids 2) MYC-mediated proliferating cells use de novo lipogenesis to produce membranes for cell growth ; Glucose and glutamine carbons are imported into cells and converted to citrate for lipogenesis ; resting T cells oxidize the de novo–.synthesized fatty acids for ATP production. Once stimulated, T cells begin to acquire nutrients, particularly glucose and glutamine, and convert them to the necessary components for making new DNA and RNA, new enzymes, new cytoskeleton, new membranes, new organelles, and new copies of genetic material

2. Nutrient sensing, FOXO, HIF, and MYC MYC function Hallmarks of cancer 2. Nutrient sensing, FOXO, HIF, and MYC - lower organisms have developed nutrient-sensing mechanisms that are coordinated with growth. Nutrient insufficiency causes decreased TORC signaling, resulting in the inhibition of the production of ribosomes and cell growth through the activation of DOT6 and TOD6 In mammalian cells; With severe starvation or pathologic processes that disrupt tissue perfusion, cell-autonomous nutrient-sensing mechanisms protect cells through pathways aimed at preserving adequate ATP pools. - The mTOR, AMP kinase (AMPK), and GCN2 pathways are key to survival of cells under nutrient deprivation. Lack of amino acids attenuates mTOR activity through sensing by the RAG proteins on the lysosomal membrane

2. Nutrient sensing, FOXO, HIF, and MYC MYC function Hallmarks of cancer 2. Nutrient sensing, FOXO, HIF, and MYC Mammalian MYC activity also depends on nutrient status sensed through mTOR via mTOR’s regulation of MYC translation nutrient sufficiency and growth factor signaling are required for MYC to carry out its transcriptional program With nutrient starvation, diminished TOR activity attenuates cell growth through diminished expression of dMyc. This pathway appears to involve TOR-dependent AKT phosphorylation

2. Nutrient sensing, FOXO, HIF, and MYC MYC function Hallmarks of cancer 2. Nutrient sensing, FOXO, HIF, and MYC With nutrient starvation, diminished TOR activity attenuates cell growth through diminished expression of dMyc. This pathway appears to involve TOR-dependent AKT phosphorylation

MYC function Hallmarks of cancer 3. Intermediary metabolism and macromolecular synthesis

MYC function Hallmarks of cancer 4. Organelle biogenesis Ribosome

Mitochondria Other organelles MYC function Hallmarks of cancer 4. Organelle biogenesis Mitochondria Other organelles

MYC function Hallmarks of cancer 5. Cell cycle progression

MYC function Hallmarks of cancer 5. Cell cycle progression

cancer therapy involved the use of anti-folates LDHA inhibitor Cancer therapy and Outlook Hallmarks of cancer cancer therapy involved the use of anti-folates LDHA inhibitor GLS inhibitor lactate exporter MCT1 inhibitor NAMPT inhibitor …. → combination therapy would be the most promising metabolic inhibition strategy in the clinic

Thank you for your attention Hallmarks of cancer Thank you for your attention