Signalna pot nuklearnega transkripcijskega faktorja kappa B

(magistrsko delo)

Mateja Žnidarić (Author), Aleš Fajmut (Mentor)

Abstract

V magistrskem delu najprej predstavimo zgradbo in delovanje nuklearnega transkripcijskega faktorja kappa B (NF-κB), ki je izražen v skoraj vseh vrstah celic. Le-ta je ob odsotnosti specifičnih stimulov latenten in se v citoplazmi nahaja v kompleksu z inhibitorjem NF-κB (IκB). Aktivira se šele pod vplivom vezave različnih stimulov na receptorje na celici, nakar začne prehajati v jedro celice, kjer se veže na DNA. To vodi do povečanega izražanja specifičnih genov. V normalnem fiziološkem stanju NF-κB inducira gene, ki imajo pomembno vlogo v procesih vnetja in tiste, ki so pomembni pri razvoju in normalnem delovanju številnih tkiv, kot so kosti, koža, mlečne žleze in centralni živčni sistem. Nepravilno delovanje signalne poti NF-κB pa lahko vodi v vnetne in avtoimune bolezni, nastanek in širjenje raka ter v rezistenco rakavih celic na kemoterapevtike. V nalogi opišemo dve najbolj znani signalni poti, preko katerih se aktivira NF-κB – klasično (kanonično) signalno pot, ki je odgovorna za kontrolo prirojene imunosti in vnetja, ter alternativno (nekanonično) signalno pot, ki ima ključno vlogo pri kontroli razvoja, organizacije in funkcije sekundarnih limfatičnih organov ter v promociji zorenja in preživetja limfocitov B. Nadalje obravnavamo matematični model, ki omogoča podrobno analizo kinetike pomembnih molekul v kanonični signalni poti: kinaz IκB (IKK), NF-κB, proteinov A20, IκBα, njihovih kompleksov in transkriptov. Ugotovimo, da se ta model v veliki meri sklada z izmerjenimi vrednostmi in z rezultati drugih modelov ter, da ob različnih pogojih in vrednostih parametrov lahko reproducira različno dinamiko sistema – oscilirajočo ali dvofazno. Identificiramo tiste parametre in njihove vrednosti, ki posledično pomembno vplivajo na časovno dinamiko izražanja genov.

Keywords

nuklearni faktor NF-kB;signalne poti;izražanje genov;matematični model;vnetje;

Data

Language:	Slovenian
Year of publishing:	2020
Typology:	2.09 - Master's Thesis
Organization:	UM FZV - Faculty of Health Sciences
Publisher:	[M. Žnidarić]
UDC:	577.112:577.2(043.2)
COBISS:	2563748
Views:	883
Downloads:	94
Average score:	0 (0 votes)
Metadata:

Other data

Secondary language:	English
Secondary title:	Signaling pathway of the nuclear transcription factor kappa B
Secondary abstract:	In the master's thesis we first present the structure and function of the nuclear transcription factor kappa B (NF-κB), which is expressed in almost all cell types. In the absence of specific stimuli, it is latent in the cytoplasm and is found in a complex with the NF-κB inhibitor (IκB). It is activated by the binding of different stimuli to the cell receptors, which induces their transport into the cell nucleus. There it binds to DNA, which leads to increased expression of specific genes. Under the normal physiological conditions, NF-κB induces genes that play an important role in the inflammation processes and those that are important in the development and normal functioning of many tissues, such as bones, skin, mammary glands, and the central nervous system. Malfunctioning of the NF-κB signaling pathway may, however, lead to inflammatory and autoimmune diseases, the emergence and spread of cancer, and the resistance of cancer cells to chemotherapeutic agents. Two of the best known signaling pathways via which NF-κB is activated are described here – the classical (canonical) pathway that is responsible for the control of innate immunity and inflammation, and the alternative (noncanonical) pathway, which plays a key role in the development control as well as in the organization and function of secondary lymphatic organs and in promoting the maturation and survival of B lymphocytes. We further discuss and study a mathematical model that allows a detailed analysis of the kinetics of important molecules in the canonical signaling pathway: kinases of IκB (IKK), NF-κB, proteins A20, IκBα, their complexes and transcripts. We find that this model is largely consistent with the measured values and the results of other models. Moreover, that under different conditions and parameter values, it can reproduce different system dynamics - oscillatory or biphasic. We identify those parameters and their values that have a significant effect on the dynamics of gene expression.
Secondary keywords:	nuclear factor NF-kB;signaling pathways;gene expression;mathematical model;inflammation;Transcription factors;Gene expression;Transkripcijski faktorji;Gensko izražanje;
Type (COBISS):	Master's thesis/paper
Thesis comment:	Univ. v Mariboru, Fak. za zdravstvene vede
Pages:	VIII, 54 f.
ID:	11339580