Genetic and cellular studies of carboxyl-ester lipase (CEL), a protein involved in exocrine and endocrine pancreatic disease
Monica Dalva Valvatne
University of Bergen, Norway 2018
Thesis for the Degree of Philosophiae Doctor (PhD)
at t h e U ni v ersit y of B er g e n
A v h a n dli n g f or gr a d e n p hil os o p hi a e d o ct or ( p h. d ) v e d U ni v ersit et et i B er g e n
.
2 0 1 7
D at o f or dis p ut as: 1 1 1 1
G e n eti c a n d c ell ul ar st u di e s of c ar b o x yl- e st er li p a s e ( C E L),
a pr ot ei n i n v ol v e d i n e x o cri n e a n d e n d o cri n e p a n cr e ati c di s e a s e
M o ni c a D al v a Val v at n e
2 0 1 8
T h esis f or t h e D e gr e e of P hil os o p hi a e D o ct or ( P h D)
Date of defe nce: 1 3. 0 9. 2 0 1 8
The material in this publication is covered by the provisions of the Copyright Act.
Print: Skipnes Kommunikasjon / University of Bergen
Title: Genetic and cellular studies of carboxyl-ester lipase (CEL), a protein involved in exocrine and endocrine pancreatic disease
© Copyright Monica Dalva Valvatne
Name: Monica Dalva Valvatne Year: 2018
expand my knowledge within the field and to “think outside the box”.
scientific discussions and “small talk breaks”
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CEL
CEL
Figure 1 Anatomy of the human pancreas
Table 1 Major digestive enzymes secreted by pancreatic acinar cells
Proteases
Amylases
α Lipases
Nucleases
Table 2 Overview of selected genes associated with chronic pancreatitis
Table 3 MODY-causing genes
–
CEL
Figure 2 Location and structure of the human carboxyl-ester lipase locus
CEL
mother’s
indispensable component of mother’s mil
In addition to CEL’s lipolytic activity, its lipoamidase activity and ability to
α β
α β β α
Figure 3 Schematic overview of the CEL protein structure
N-terminal domain: Structure-function relations
α
C-terminal domain: Structure-function relations
Common secretory pathway of digestive enzymes
Specific co- and post-translational modifications during intracellular transport of CEL
Figure 4 Secretory pathway of CEL
Internalization of CEL
Figure 5 Endocytosis of secreted CEL by enterocytes
Figure 6 Schematic structures of the MODY8-associated variants
κ
Figure 7 Schematic structure of the pathogenic CEL CNV: CEL-HYB
“only”
r’s disease, cancer and atherosclerosis
r’s disease, the net balance between
neurotoxic Aβ fibrils. Intracellular accumulation of these aggregated fib then result in the development of Alzheimer’s disease (reviewed in
CEL
Figure 8 Genetic variability of CEL
’
F2α branch of the UPR, as increased levels of phosphorylated eIF2α
phosphorylation of eIF2α is a pathway of
eIF2α branch of the UPR
Figure 9 Internalized CEL-MODY and CEL-HYB proteins might trigger apoptosis through overlapping and distinct routes
eIF2α branch of the UPR
CEL –
Graphic design: Communication Division, UiB / Print: Skipnes Kommunikasjon AS
