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Nutrigenomics

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Carsten Carlberg · Stine Marie Ulven
Ferdinand Molnár

Nutrigenomics
Nutrigenomics
Carsten Carlberg • Stine Marie Ulven
Ferdinand Molnár

Nutrigenomics
Carsten Carlberg Stine Marie Ulven
Institute of Biomedicine Department of Nutrition
University of Eastern Finland University of Oslo
Kuopio, Finland Oslo, Norway

Ferdinand Molnár
School of Pharmacy
University of Easterm Finland
Kuopio, Finland

ISBN 978-3-319-30413-7 ISBN 978-3-319-30415-1 (eBook)

DOI 10.1007/978-3-319-30415-1

Library of Congress Control Number: 2016939131

© Springer International Publishing Switzerland 2016

This work is subject to copyright. All rights are reserved by the Publisher, whether the whole or part of
the material is concerned, specifically the rights of translation, reprinting, reuse of illustrations, recitation,
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The use of general descriptive names, registered names, trademarks, service marks, etc. in this publication
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The publisher, the authors and the editors are safe to assume that the advice and information in this book
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Printed on acid-free paper

This Springer imprint is published by Springer Nature

The registered company is Springer International Publishing AG Switzerland
Preface

Our daily diet is more than a collection of carbohydrates, lipids and proteins that
provide energy and serve as building blocks of our life; our diet is also the most
dominant environmental signal to which we are exposed from womb to death. The
fascinating area of nutrigenomics analyses this daily communication between diet,
food and nutrients, their metabolites and our genome. This book describes how
nutrition shapes human evolution and demonstrates its consequences for our sus-
ceptibility to diseases, such as diabetes and atherosclerosis. Inappropriate diet can
yield stress for our cells, tissues and organs and then it is often associated with low-
grade chronic inflammation. Overnutrition paired with physical inactivity leads to
overweight and obesity and results in increased burden for a body that originally
was adapted for a life in the savannas of East Africa. Therefore, this textbook does
not discuss a theoretical topic in science, but it talks about real life and our life-long
“chat” with diet. We are all food consumers, thus each of us is concerned by the
topic of this book and should be aware of its mechanisms.
The availability of the sequence of the complete human genome and the conse-
quent development of next-generation sequencing technologies have significantly
affected nearly all areas of bioscience. This new knowledge was the starting point
for new disciplines, such as genomics and its sub-discipline nutrigenomics. The lat-
ter comprises not only the variation of the human genome, such as single nucleotide
polymorphisms (SNPs), but also the dynamic packaging of the genome into chro-
matin including all information stored in this epigenome. Moreover, this book
describes the proteins that are involved in the signal transduction between dietary
molecules and the genome, such as nuclear receptors, chromatin modifiers and
energy status-sensing kinases, and their mechanism of action.
The purpose of this book is to provide an overview on the principles of nutrige-
nomics and their relation to health or disease. We are not aiming to compete with
more comprehensive textbooks on molecular nutrition, evolutionary biology, geno-
mics, gene regulation or metabolic diseases, but rather will focus on the essentials
and will combine, in a compact form, elements from different disciplines. In order
to facilitate the latter, we favour a high figure-to-text ratio following the rule “a pic-
ture tells more than thousand words”.

v
vi Preface

The content of this book is based on the lecture course “Nutrigenomics”, which
is held since 2003 once per year by one of us (C. Carlberg) at the University of
Eastern Finland in Kuopio. The book is subdivided into 3 sections and 12 chapters.
Following the “Introduction”, there are sections on the “Molecular genetic basis”
and the “Links to disease”, which take a view on nutrigenomics from the perspec-
tive of molecular mechanisms or from the causes of metabolic diseases,
respectively.
This book is primarily designed for master level students of biosciences, but may
also be used by students of other biomedical disciplines and by PhD students. The
book has five major learning objectives. Students should:
(i) Get an overview on human variation on the level of the genome and epigenome,
in response to dietary molecules and the regulatory proteins involved in the
respective signal transduction processes
(ii) Have an understanding of the diseases that are strongly associated with dietary
intake and physical inactivity, such as obesity, type 2 diabetes, atherosclerosis
and the metabolic syndrome
(iii) Recognize the key components and mechanisms in nutrigenomics and the mul-
tiple layers of its regulatory complexity
(iv) Show the ability to analyze the human genome and epigenome and its variation
in nutrition sensing and information processing processes, i.e. to judge their
impact for on the complex etiology of metabolic diseases
(v) Apply knowledge in nutrigenomics in designing, performing and analyzing
respective experiments, such as quantitative PCR, RNA-seq or ChIP-seq
We hope the readers will enjoy this demonstrative book and get as enthusiastic
about the topic of nutrigenomics as the authors do.

Kuopio and Oslo Carsten Carlberg

December 2015 Stine Marie Ulven
Ferdinand Molnár
Acknowledgements

The authors would like to thank Reinhard Bornemann, MD, PhD, Marjukka
Kolehmainen, PhD, Vibeke Telle-Hansen, PhD, and Jenni Puurunen, MSc, for
extensive proofreading and constructive criticism.

vii
Contents

Part I Introduction
1 Nutrition and Common Diseases ........................................................... 3
1.1 Human Nutrition ............................................................................ 3
1.2 Nutrition and Obesity ..................................................................... 8
1.3 Nutrition and Cancer ...................................................................... 9
1.4 Nutrition and Diabetes ................................................................... 11
1.5 Nutrition and Cardiovascular Diseases .......................................... 13
1.6 Impact of Exercise.......................................................................... 20
Additional Reading ................................................................................... 23
2 Human Genomic Variation .................................................................... 25
2.1 Migration and Evolutionary Challenges of the Modern
Human ............................................................................................ 26
2.2 Diversity of Human Populations .................................................... 27
2.3 Genetic Variants of the Human Genome ........................................ 30
2.4 The HapMap Project and Haplotype Blocks ................................. 33
2.5 Genome-wide Association Studies................................................. 35
2.6 Whole Genome Sequencing and the 1000 Genomes
Project ............................................................................................ 40
Additional Reading ................................................................................... 44

Part II Molecular Genetic Basis

3 Sensing Nutrition .................................................................................... 47
3.1 Nutrient-Sensing Mechanisms ....................................................... 48
3.2 Nutrient Sensing via Nuclear Receptors ........................................ 51
3.3 Functions and Actions of PPARs ................................................... 56
3.4 Integration of Lipid Metabolism by LXRs and FXR ..................... 58
3.5 Coordination of the Immune Response by VDR ........................... 61
3.6 Circadian Control of Metabolic Processes ..................................... 64
Additional Reading ................................................................................... 69

ix
x Contents

4 Adaption of the Human Genome to Dietary Changes ......................... 71

4.1 Definition of Nutrigenomics .......................................................... 72
4.2 Vitamin D and Skin Color .............................................................. 72
4.3 Human Genetic Adaption to Dietary Changes ............................... 76
4.4 Regulatory SNPs and Quantitative Traits ...................................... 77
4.5 “Omics” Analysis in Nutrition Sciences ........................................ 80
4.6 Integrative Personal Omics Profile................................................. 83
Additional Reading ................................................................................... 86
5 Nutritional Epigenomics......................................................................... 87
5.1 Epigenetics Mechanisms ................................................................ 88
5.2 Intermediary Metabolism and Epigenetic Signaling ...................... 91
5.3 One-Carbon Metabolism and DNA Methylation ........................... 94
5.4 Nutrition-Triggered Transgenerational Epigenetics
in Mice ........................................................................................... 96
5.5 Epigenetic Programming in Humans ............................................. 98
Additional Reading ................................................................................... 104
6 Nutritional Signaling and Aging ............................................................ 105
6.1 Aging and Conserved Nutrient-Sensing Pathways ........................ 106
6.2 Neuroendocrine Aging Regulation in Humans
and Other Mammals ....................................................................... 109
6.3 Calorie Restriction from Yeast to Mammals .................................. 110
6.4 Properties and Functions of Sirtuins .............................................. 113
6.5 Cellular Energy Status Sensing by AMPK..................................... 117
Additional Reading ................................................................................... 120
7 Chronic Inflammation and Metabolic Stress ....................................... 121
7.1 The Central Role of Monocytes and Macrophages ........................ 121
7.2 Acute and Chronic Inflammation ................................................... 124
7.3 Reverse Cholesterol Transport and Inflammation .......................... 128
7.4 M1 and M2 Macrophages in Adipose Tissue ................................. 131
7.5 ER Stress Response ........................................................................ 133
Additional Reading ................................................................................... 137

Part III Links to Diseases

8 Obesity ..................................................................................................... 141
8.1 Definition of Obesity ...................................................................... 141
8.2 Adipogenesis .................................................................................. 145
8.3 Energy Homeostasis ....................................................................... 148
8.4 Hormonal Regulation of Food Anticipation................................... 150
8.5 Adipose Tissue is an Endocrine Organ .......................................... 152
8.6 Inflammation in Adipose Tissue ..................................................... 155
8.7 Genetics of Obesity ........................................................................ 157
Additional Reading ................................................................................... 161
Contents xi

9 Glucose Homeostasis, Insulin Resistance and β Cell Failure .............. 163

9.1 Glucose Homeostasis in Health ..................................................... 164
9.2 Principles of Insulin Signaling ....................................................... 167
9.3 Central Role of FOXO Transcription Factors ................................ 169
9.4 Insulin Resistance in Skeletal Muscle and Liver ........................... 173
9.5 β Cell Failure .................................................................................. 176
Additional Reading ................................................................................... 180
10 Diabetes .................................................................................................... 181
10.1 Definition of Diabetes .................................................................... 181
10.2 Failure of Glucose Homeostasis in T2D and Its Treatment ........... 185
10.3 Genetics of T2D ............................................................................. 188
10.4 Thrifty Gene Hypothesis ................................................................ 191
Additional Reading ................................................................................... 193
11 Hypertension, Atherosclerosis and Dyslipidemias ............................... 195
11.1 Hypertension .................................................................................. 195
11.2 Mechanisms of Atherosclerosis...................................................... 197
11.3 Cholesterol Metabolism and Lipoproteins ..................................... 202
11.4 Dyslipidemias................................................................................. 205
Additional Reading ................................................................................... 208
12 The Metabolic Syndrome ....................................................................... 209
12.1 Definitions of the Metabolic Syndrome ......................................... 209
12.2 Whole Body’s Perspective on the Metabolic Syndrome ................ 212
12.3 Metabolic Syndrome in Key Metabolic Organs............................. 212
12.4 Genetic and Epigenetic Basis of the Metabolic Syndrome ............ 217
Additional Reading ................................................................................... 222
Abbreviations

1,25(OH)2D3 1,25-dihydroxyvitamin D3
25(OH)D3 25-hydroxyvitamin D3
5,10-MTHF 5,10-methylene THF
α-MSH α-melanocyte-stimulating hormone
ABC ATP-binding cassette
ABL abetalipoproteinemia
AC adenylate cyclase
ACAT1 acetyl-CoA acetyltransferase 1
ACC acetyl-CoA carboxylase
ACL ATP citrate lyase
ADRB3 adrenoceptor beta 3
AGRP agouti-related peptide
AKT Akt murine thymoma viral oncogene homolog
ALA α-linolenic acid
ALOX5 arachidonate 5-lipoxygenase
ALOX15 arachidonate 15-lipoxygenase
AMPK adenosine monophosphate-activated protein kinase
AMY1 amylase
ANGPTL2 angiopoietin-like protein 2
APEH N-acylaminoacyl-peptide hydrolase
AP-1 activating protein 1
APO apolipoprotein
AR androgen receptor
ARL4C ADP-ribosylation factor-like
ARNTL aryl hydrocarbon receptor nuclear translocator-like
ASC apoptosis-associated speck
ASIP agouti signaling protein
ATF6 activating transcription factor 6
ATM ataxia telangiectasia mutated
atRA all-trans retinoic acid
β-OHB β-hydroxybutyrate

xiii
xiv Abbreviations

BAAT bile acid-CoA-amino acid N-acetyltransferase

BAT brown adipose tissue
BDNF brain-derived neurotrophic factor
BLK B lymphoid tyrosine kinase
BMD bone mineral density
BMI body mass index
BMP bone morphogenetic protein
bp base pair
CAMKK Ca2+/calmodulin-dependent protein kinase kinase
CAMP cathelicidin anti-microbial peptide
CAR constitutively androstane receptor
CASP caspase
CBL Cbl proto-oncogene, E3 ubiquitin protein ligase
CBP CREB-binding protein
CCL chemokine (C-C motif) ligand
CCR C-C chemokine receptor
CD36 CD36 molecule
CDC42 cell-division cycle 42
CDKAL1 CDK5 regulatory subunit associated protein 1-like 1
CDKN cyclin-dependent kinase inhibitor
CDP common dendritic cell progenitor
CEBP CCAAT-binding protein
CEL carboxyl ester lipase
CETP cholesterol ester transfer protein
CHD coronary heart disease
ChIP chromatin immunoprecipitation
CITED1 CBP/p300-interacting transactivator 1
CLOCK clock circadian regulator
CNR cannabinoid receptor 1
CNS central nervous system
CNV copy number variant
CPT1A carnitine palmitoyltransferase 1A
CREB3L3 cAMP responsive element binding protein 3-like 3
CRP C-reactive protein
CRTC2 CREB-regulated transcription co-activator 2
CRY1 cryptochrome circadian clock 1
CSF2 colony stimulating factor 2
CVD cardiovascular disease
CXCL5 chemokine (C-X-C motif) ligand 5
CXCR2 CXC-chemokine receptor 2
CYP cytochrome P450
D2HGDH D-2-hydroxyglutarate dehydrogenase
DAG diacylglycerol
DALY disability-adjusted life-year
DAMP damage-associated molecular pattern
Abbreviations xv

DGAT1 diacylglycerol O-acyltransferase 1

DHA docosahexaenoic acid
DHF dihydrofolate
DEFB4 defensin, beta 4A
DNMT DNA methyltransferase
EHMT1 euchromatic histone-lysine N-methyltransferase 1
EGIR European Group for the study of Insulin Resistance
EIF2A eukaryotic translation initiation factor 2A
EIF2AK3 eukaryotic translation initiation factor 2-alpha kinase 3
ENCODE encyclopedia of DNA elements
ENPP1 ectonucleotide pyrophosphatase/phosphodiesterase 1
EPA eicosapentaenoic acid
EPIC European Prospective Investigation into Cancer and Nutrition
eQTL expression quantitative trait locus
ER endoplasmatic reticulum
ERN1 endoplasmic reticulum to nucleus signaling 1
ES cell embryonic stem cell
E% percent of total energy
FABP6 ileal fatty acid-binding protein 6
FAD flavin adenine dinucleotide
FAIRE formaldehyde-assisted isolation of regulatory elements
FAO Food and Agriculture Organization
FAS Fas cell surface death receptor
FASN fatty acid synthase
FFA free fatty acid
FGF fibroblast growth factor
FGFR4 FGF receptor 4
FH fumarate hydratase
FOX forkhead box
FTO fat mass and obesity associated
FXR farnesoid X receptor
G6PC glucose-6-phosphatase
GAB1 GRB2-associated binder 1
GCK glucokinase
GC-MS gas chromatography-mass spectrometry
GDH glutamate dehydrogenase
GH growth hormone
GLP1 glucagon-like peptide 1
GO gene ontology
GPAT glycerol phosphate acyl transferase
GPR G-protein-coupled receptor
GR glucocorticoid receptor
GRB growth factor receptor-bound protein
GS glycogen synthase
GSK3 glycogen synthesis kinase 3
xvi Abbreviations

GWAS genome-wide association study

HAT histone acetyltransferase
HDAC histone deacetylase
HDM histone demethylase
HDL high-density lipoprotein
HHEX hematopoietically expressed homeobox
HIF1α hypoxia-inducible factor 1α
HIV human immunodeficiency virus
HLA human leukocyte antigen
HMGCR 3-hydroxy-3-methylglutaryl-CoA reductase
HMGCS2 3-hydroxy-3-methylglutaryl-CoA synthase 2
HMT histone methyltransferase
HNF hepatocyte nuclear factor
HPT hypothalamic-pituitary-thyroid
HSF1 shock transcription factor 1
HSP heat-shock protein
HTG hypertriglycerolemia
IAP intracisternal A particle
ICAM1 intercellular adhesion molecule 1
IDF International Diabetes Federation
IDH isocitrate dehydrogenase
IDOL inducible degrader of LDLR
IFG impaired fasting glucose
IFNγ interferon gamma
IGF insulin-like growth factor
IGF1R IGF1 receptor
IGF2BP2 insulin-like growth factor 2 mRNA binding protein 2
IGT impaired glucose tolerance
IKBK inhibitor of kappa light polypeptide gene enhancer in B cells, kinase
IL interleukin
IL1R IL1 receptor
IL1RN IL1 receptor antagonist
indel insertion-deletion variant
IR insulin receptor
IRF3 interferon-regulatory factor 3
IRS insulin receptor substrate
IRX3 iroquois homeobox 3
ITGA4 integrin, alpha 4
ITGB2 integrin, beta 2
IVF in vitro fertilization
JAK Janus kinase
KATP ATP-sensitive K+
kb kilobase
KEAP1 kelch-like ECH-associated protein 1
KLF Krüppel-like factor
Abbreviations xvii

KCNJ11 potassium inwardly rectifying channel, subfamily J, member 11

LA linolenic acid
LBD ligand-binding domain
LCAD long-chain acyl-CoA dehydrogenase
LCAT lecithin cholesterol acyltransferase
LCT lactase
LDL low-density lipoprotein
LDLR LDL receptor
LDLRAP1 LDLR accessory protein 1
LEP leptin
LEPR leptin receptor
LIPC hepatic lipase
LIPE hormone sensitive lipase
LIPG endothelial lipase
LINE long interspersed element
LPCAT3 lysophospholipid acyltransferase 3
LPL lipoprotein lipase
LRH-1 liver receptor homolog 1
LRP1 LDLR-related protein 1
LXR liver X receptor
MAF minor allele frequency
MAFA v-maf avian musculoaponeurotic fibrosarcoma oncogene homolog A
MAN2A1 mannosidase, alpha, class 2A, member 1
MAP mitogen-activated protein
MAPK8 mitogen-activated protein kinase 8 (also called JNK)
MC4R melanocortin 4 receptor
M-CFU myeloid stem cells
MCM6 minichromosome maintenance type 6
MDH malate dehydrogenase
MDP macrophage and dendritic cell progenitor
MECP2 methyl-CpG-binding protein 2
MED mediator
MHC major histocompatibility complex
miRNA micro RNA
MLXIPL MLX interacting protein-like
mmHg millimeters of mercury
MODY maturity onset diabetes of the young
MPO myeloperoxidase
MR mineralocorticoid receptor
mRNA messenger RNA
MSR1 macrophage scavenger receptor 1
MTHFR methylenetetrahydrofolate reductase
MTNR1B melatonin receptor 1B
mTORC mammalian target of rapamycin complex
MTTP microsomal triglycerole transfer protein
xviii Abbreviations

MYCL v-myc avian myelocytomatosis viral oncogene lung carcinoma

derived homolog
MYD88 myeloid differentiation primary response protein 88
MYF5 myogenic factor 5
NAD nicotinamide adenine dinucleotide
NAFLD non-alcoholic fatty liver disease
NAMPT nicotinamide mononucleotide phosphoribosyltransferase (also called
visfatin)
NANOG NANOG homeobox
NCEH1 neutral cholesterol ester hydrolase 1
NCOA nuclear receptor coactivator
NCEP National Cholesterol Education Program
ncRNA non-coding RNA
NEUROD1 neuronal differentiation 1
NF-κB nuclear factor κB
NLRP NLR protein
NLR NOD-like receptor
NO nitric oxide
NOS2 inducible nitric oxide synthase 2
NPC1L1 Niemann-Pick C1-like protein 1
NPY neuropeptide Y
NRIP1 nuclear receptor interacting protein 1
NSAID non-steroidal anti-inflammatory drug
NTS nucleus tractor solitarius
OAADR O-acetyl ADP-ribose
O-GlcNAc O-linked N-acetylglucosamine
OGA O-GlcNAcase
OGT O-GlcNAc transferase
OGTT oral glucose tolerance test
PAMP pathogen-associated molecular pattern
PAX paired box
PC pyruvate carboxylase
PCK phosphoenolpyruvate carboxykinase
PCSK1 POMC proprotein convertase subtilisin/kexin type 1
PDH pyruvate dehydrogenase
PDPK 3-phosphoinositide dependent protein kinase
PDX1 pancreatic and duodenal homeobox 1
PER1 period circadian clock 1
PFKFB2 6-phosphofructo-2-kinase/fructose-2,6-biphosphatase 2
PGE2 prostaglandin E2
PH pleckstrin-homology
PI3K phosphoinositide 3-kinase
PIP3 phosphatidylinositol-3,4,5-triphosphate
PKA protein kinase A
PLAU plasminogen activator, urokinase
Abbreviations xix

PLTP phospholipid transfer protein

PNPLA patatin-like phospholipase domain containing
Pol II RNA polymerase II
POMC pro-opiomelanocortin
POU5F1 POU class 5 homeobox 1
PPAR peroxisome proliferator-activated receptor
PPARGC1A PPAR gamma, coactivator 1 alpha
PPP2 protein phosphatase 2
PRDM16 PR domain containing 16
PRR pattern recognition receptor
PUFA polyunsaturated fatty acid
PTB phosphotyrosine-binding
PTEN phosphatase and tensin homologue
PTGS2 prostaglandin-endoperoxide synthase 2 (also known as COX2)
PTPN1 protein tyrosine phosphatase, non-receptor type 1
PVN paraventricular nuclei
PXR pregnane X receptor
qPCR quantitative PCR
RAPTOR regulatory associated protein of TOR
RAR retinoic acid receptor
RBP4 retinol binding protein 4
RE response element
REV-ERB Reverse-Erb
RHEB Ras homolog enriched in brain
RHOQ Ras homolog family, member Q
RIG1 retinoic acid-inducible gene 1
RLR RIG1-like helicase receptors
RNAi RNA interference
ROR RAR-related orphan receptor
ROS reactive oxygen species
RRAG Ras-related GTP binding
RPS6K ribosomal protein S6 kinase
RXR retinoid X receptor
S6K S6 kinase
SAH S-adenosylhomocysteine
SAM S-adenosylmethionine
SCAP SREBF chaperone
SCD1 steroyl-CoA desaturase 1
SCN suprachiasmatic nucleus
SCNN1 sodium channel, non-voltage-gated 1
SDH succinate dehydrogenase
SEC16B SEC16 homolog B
SERPINE1 serpin peptidase inhibitor, clade E (also called PAI-1)
SF-1 steroidogenic factor 1
SFA saturated fatty acids
xx Abbreviations

SFRP5 frizzled-related protein 5

SHC Src homology 2 domain containing
SI sucrase-isomaltase
SIM1 single-minded family bHLH transcription factor 1
SINE short interspersed element
siRNA small interfering RNA
Sir2 silent information regulator 2
SIRT sirtuin
SLC solute carrier
SLCO solute organic anion transporter
SLK STE20-like kinase
SNP single nucleotide polymorphism
SNS sympathetic nervous system
SOCS3 suppressor of cytokine signaling 3
SOD2 superoxide dismutase 2
SORBS1 sorbin and SH3 domain containing 1
SOS son of sevenless
SPI1 spleen focus forming virus proviral integration oncogene (also
called PU.1)
SREBF1 sterol regulatory element-binding transcription factor 1
STAT signal transducer and activator of transcription
SULT2A1 sulfotransferase family 2A, member 1
T1D type 1 diabetes
T2D type 2 diabetes
TAS1R2 taste receptor, type 1, member 2
TBC1D TBC1 domain family, member 1
TBP TATA-box binding protein
TCA tricarboxylic acid
TD Tangier disease
TET ten-eleven translocation
TGFB1 transforming growth factor beta 1
TH T helper
THF tetrahydrofolate
THRSP thyroid hormone responsive
TIFIA transcription initiation factor IA
TLR Toll-like receptor
TMEM18 transmembrane protein 18
TNF tumor necrosis factor
TNFR TNF receptor
TOR target of rapamycin
TRAF2 TNF receptor-associated factor 2
TREG regulatory T
TSC2 tuberous sclerosis 2
TSS transcription start site
UBR1 ubiquitin protein ligase E3 component n-recognin 1
Abbreviations xxi

UDP uridine diphosphate

UCP uncoupling protein
UGT2B4 UDP glucuronosyltransferase 2 family, polypeptide B4
UNC5B unc-5 homolog B
UTR untranslated region
UV ultraviolet
VCAM1 vascular cell adhesion molecule 1
VDR vitamin D receptor
VLDL very low-density lipoprotein
VNN1 vanin 1
WAT white adipose tissue
WHO World Health Organization
WHR waist-hip ratio
YWHA tyrosine 3-monooxygenase/tryptophan 5-monooxygenase activa-
tion protein (also called 14-3-3)
XBP1 X-box binding protein 1
 Part I
Introduction

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