TY  - GEN
UR  - https://archiv.ub.uni-heidelberg.de/volltextserver/24155/
N2  - Th? ?nt?-v?r?l cyt?k?n? ?nt?rf?r?n ?lph? (?FN?) ?s us?d f?r th? tr??tm?nt ?f chr?n?c H?p?t?t?s B ?nd C ?nd v?r??us typ?s ?f c?nc?rs. ?ft?n p?t??nts d? n?t r?sp?nd t? th? tr??tm?nt wh?ch h?s b??n c?rr?l?t?d t? pr?-?ct?v?t??n ?f ?FN?-?nduc?d s?gn?l?ng, ?s ?ss?ss?d by ?nh?nc?d ?xpr?ss??n ?f ?FN? t?rg?t g?n?s. ?FN? ?ct?v?t?s th? J?K/ST?T s?gn?l tr?nsduct??n p?thw?y, wh?ch ?nv?lv?s n?g?t?v? f??db?ck l??ps m?d??t?d by S?CS1, S?CS3 ?nd USP18 ?nd p?s?t?v? f??db?ck l??ps m?d??t?d by ?RF9, ST?T1 ?nd ST?T2. Th? ?bj?ct?v? ?f th?s study w?s t? ?nv?st?g?t? ?f th? dyn?m?c b?h?v??r ?f ?FN?-?nduc?d s?gn?l tr?nsduct??n ?s ?ff?ct?d ?n ?FN? pr?-tr??t?d c?lls ?nd t? d?ss?ct th? m?ch?n?sm c?ntr?but?ng t? ? p?ss?bl? m?m?ry ?ff?ct ?f pr?-?ct?v?t??n ?f ?FN?-?nduc?d s?gn?l tr?nsduct??n. Th?s? ??ms w?r? ?ppr??ch?d by c?mb?n?ng qu?nt?t?t?v? t?m?- ?nd d?s?-r?s?lv?d d?t? ?f ?FN?-?nduc?d s?gn?l?ng ?n h?p?t?m? c?ll l?n?s ?nd pr?m?ry hum?n h?p?t?cyt?s w?th m?th?m?t?c?l m?d?l?ng.
T? ?x?m?n? th? ?ff?ct ?f pr?-?ct?v?t??n ?f th? ?FN?-?nduc?d s?gn?l?ng tr?nsduct??n, c?lls w?r? pr?-tr??t?d w?th d?ff?r?nt d?s?s ?f ?FN?, w?r? st?mul?t?d w?th ? h?gh d?s? ?f ?FN? ?nd th? dyn?m?c?l b?h?v??r ?f ?FN?-?nduc?d s?gn?l?ng w?s ?n?lyz?d by qu?nt?t?t?v? ?mmun?bl?tt?ng. Th? ?bt??n?d r?sults r?v??l?d th?t pr?-tr??tm?nt w?th ? l?w d?s? ?f ?FN? r?sult?d ?n ?nh?nc?d ?FN?-?nduc?d ph?sph?ryl?t??n ?f ST?T1 ?nd ST?T2 ?bs?rv?d ?n th? nucl?us, wh?l? pr?-tr??tm?nt w?th ? h?gh d?s? ?f ?FN? r?sult?d ?n much r?duc?d ?FN?-?nduc?d ph?sph?ryl?t??n ?f ST?T1 ?nd ST?T2 ?n th? cyt?pl?sm ?nd ?n th? nucl?us, ?nd?c?t?ng ? p?s?t?v? ?nd n?g?t?v? m?m?ry ?f ?FN?-?nduc?d s?gn?l tr?nsduct??n, r?sp?ct?v?ly. Th? ?n?lys?s ?f ?FN?-?nduc?d g?n? ?xpr?ss??n sh?w?d th?t n?g?t?v? m?m?ry ?f ?FN?-?nduc?d s?gn?l tr?nsduct??n pr?v?nt?d n? furth?r ?nduct??n ?f ?FN?-?nduc?d g?n? ?xpr?ss??n, wh?l? p?s?t?v? m?m?ry r?sult?d ?n f?st?r g?n? ?xpr?ss??n ?f ?FN?-t?rg?t g?n?s.
T? unr?v?l th? m?ch?n?sms c?ntr?but?ng t? p?s?t?v? ?nd n?g?t?v? m?m?ry ?f ?FN?-?nduc?d s?gn?l tr?nsduct??n, ? m?th?m?t?c?l m?d?l w?s ?st?bl?sh?d ?nd c?l?br?t?d w?th t?m?- ?nd d?s?-r?s?lv?d d?t? c?mpr?s?ng pr?-tr??tm?nt w?th d?ff?r?nt d?s?s ?f ?FN? ?nd subs?qu?nt ?FN? st?mul?t??n t? ch?r?ct?r?z? th? ?nduct??n ?f th? p?s?t?v? ?nd th? n?g?t?v? f??db?ck l??ps. ?xp?r?m?nts sh?w?d th?t ?RF9, ST?T1 ?nd ST?T2 ?r? ?nduc?d ?t l?w?r ?FN? d?s?s c?mp?r?d t? USP18, S?CS1 ?nd S?CS3. T? ?n?lyz? th? sp?c?f?c r?l? ?f USP18, USP18 ?xpr?ss??n w?s ?nduc?d t? th? s?m? ?m?unt ?s pr?s?nt ?n c?lls pr?-tr??t?d w?th ? h?gh d?s? ?f ?FN?, ?FN?-?nduc?d ph?sph?ryl?t??n ?f ST?T1 ?nd ST?T2 w?s l?w?r c?mp?r?d t? w?ldtyp? c?lls, but much h?gh?r c?mp?r?d t? c?lls pr?-tr??t?d w?th ? h?gh d?s? ?f ?FN?, ?nd?c?t?ng th?t USP18 ?bund?nc? ?l?n? ?s n?t suff?c??nt t? ?xpl??n th? n?g?t?v? m?m?ry ?f ?FN?-?nduc?d s?gn?l tr?nsduct??n. M?th?m?t?c?l m?d?l ?n?lys?s r?v??l?d th?t S?CS1 ?nd USP18 t?g?th?r syn?rg?st?c?lly ?nh?nc? d?gr?d?t??n ?f ?ct?v? r?c?pt?r c?mpl?x?s ?nd th?r?by much r?duc?d th? ?FN?-?nduc?d ph?sph?ryl?t??n ?f ST?T1 ?nd ST?T2. M?d?l ?n?lys?s ?f th? p?s?t?v? m?m?ry ?d?nt?f??d ST?T2 ?nd ?RF9 ?s k?y c?ntr?but?rs. M?d?l s?mul?t??ns pr?d?ct?d th?t th? ?bund?nc? ?f ST?T2 ?nd USP18 t?g?th?r, but n?t ?f S?CS1, ?s suff?c??nt t? pr?d?ct th? d?r?ct??n ?nd ?xt?nt ?f th? m?m?ry ?f ?FN?-?nduc?d s?gn?l tr?nsduct??n. Qu?nt?f?c?t??n ?f th? ?m?unt ?f ST?T2 ?nd USP18 ?n pr?m?ry hum?n h?p?t?cyt?s fr?m thr?? d?ff?r?nt p?t??nts ?d?nt?f??d h?gh p?t??nt-t?-p?t??nt-v?r??b?l?ty ?n th? ?m?unt ?f USP18, but n?t ?f ST?T2. Th?r?f?r?, USP18 ?bund?nc? w?s ?d?nt?f??d ?nd ?xp?r?m?nt?lly v?l?d?t?d ?s p?t??nt-sp?c?f?c ?nd?c?t?r ?f m?m?ry ?f ?FN? s?gn?l tr?nsduct??n, pr?v?d?ng n?w p?rsp?ct?v?s f?r ?pt?m?l d?s?ng ?f ?FN? th?t w?uld pr?v?nt n?n-r?sp?ns?v?n?ss t? ?FN? tr??tm?nt ?n ?nd?v?du?l p?t??nts.
TI  - Disentangling mechanisms of positive and negative memory of interferon alpha signal transduction
AV  - public
ID  - heidok24155
A1  - Kok, Frédérique
Y1  - 2018///
ER  -