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Pathway Description
Peginterferon alfa-2b Action Pathway
Homo sapiens
Drug Action Pathway
Created: 2023-05-12
Last Updated: 2023-10-25
Peginterferon alfa-2b, also known as Pegintron or Sylatron, is a purified recombinant human interferon. It is used as part of combination therapy to treat chronic Hepatitis C caused by the Hepatitis C Virus (HCV). It is also used as an adjuvant treatment of melanoma with microscopic or gross nodal involvement within 84 days of definitive surgical resection. The mechanism of action is the inhibition of the viral replication in infected cells caused by the binding of the peginterferon to the human type 1 interferon receptors causing them to dimerize. This, in consequence, activates the JAK-STATS pathway which increases the expression of multiple genes involved in the innate antiviral response. Its immunomodulatory effects are the enhancement of the phagocytic activity, the activation of NK cells, the stimulation of cytotoxic T-lymphocytes, and the upregulation of the Th1 T-helper cell subset.
References
Peginterferon alfa-2b Pathway References
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Pubmed: 28497432
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Pubmed: 15898717
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Pubmed: 16953837
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Pubmed: 11752352
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Pubmed: 9630560
Tsai YT, Su YH, Fang SS, Huang TN, Qiu Y, Jou YS, Shih HM, Kung HJ, Chen RH: Etk, a Btk family tyrosine kinase, mediates cellular transformation by linking Src to STAT3 activation. Mol Cell Biol. 2000 Mar;20(6):2043-54. doi: 10.1128/mcb.20.6.2043-2054.2000.
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Pubmed: 12359225
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Pubmed: 19361440
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Pubmed: 1848670
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Pubmed: 16710414
Peeters P, Raynaud SD, Cools J, Wlodarska I, Grosgeorge J, Philip P, Monpoux F, Van Rompaey L, Baens M, Van den Berghe H, Marynen P: Fusion of TEL, the ETS-variant gene 6 (ETV6), to the receptor-associated kinase JAK2 as a result of t(9;12) in a lymphoid and t(9;15;12) in a myeloid leukemia. Blood. 1997 Oct 1;90(7):2535-40.
Pubmed: 9326218
Reiter A, Walz C, Watmore A, Schoch C, Blau I, Schlegelberger B, Berger U, Telford N, Aruliah S, Yin JA, Vanstraelen D, Barker HF, Taylor PC, O'Driscoll A, Benedetti F, Rudolph C, Kolb HJ, Hochhaus A, Hehlmann R, Chase A, Cross NC: The t(8;9)(p22;p24) is a recurrent abnormality in chronic and acute leukemia that fuses PCM1 to JAK2. Cancer Res. 2005 Apr 1;65(7):2662-7. doi: 10.1158/0008-5472.CAN-04-4263.
Pubmed: 15805263
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Pubmed: 16424865
Rogers RS, Horvath CM, Matunis MJ: SUMO modification of STAT1 and its role in PIAS-mediated inhibition of gene activation. J Biol Chem. 2003 Aug 8;278(32):30091-7. doi: 10.1074/jbc.M301344200. Epub 2003 May 22.
Pubmed: 12764129
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Pubmed: 1502203
Ota T, Suzuki Y, Nishikawa T, Otsuki T, Sugiyama T, Irie R, Wakamatsu A, Hayashi K, Sato H, Nagai K, Kimura K, Makita H, Sekine M, Obayashi M, Nishi T, Shibahara T, Tanaka T, Ishii S, Yamamoto J, Saito K, Kawai Y, Isono Y, Nakamura Y, Nagahari K, Murakami K, Yasuda T, Iwayanagi T, Wagatsuma M, Shiratori A, Sudo H, Hosoiri T, Kaku Y, Kodaira H, Kondo H, Sugawara M, Takahashi M, Kanda K, Yokoi T, Furuya T, Kikkawa E, Omura Y, Abe K, Kamihara K, Katsuta N, Sato K, Tanikawa M, Yamazaki M, Ninomiya K, Ishibashi T, Yamashita H, Murakawa K, Fujimori K, Tanai H, Kimata M, Watanabe M, Hiraoka S, Chiba Y, Ishida S, Ono Y, Takiguchi S, Watanabe S, Yosida M, Hotuta T, Kusano J, Kanehori K, Takahashi-Fujii A, Hara H, Tanase TO, Nomura Y, Togiya S, Komai F, Hara R, Takeuchi K, Arita M, Imose N, Musashino K, Yuuki H, Oshima A, Sasaki N, Aotsuka S, Yoshikawa Y, Matsunawa H, Ichihara T, Shiohata N, Sano S, Moriya S, Momiyama H, Satoh N, Takami S, Terashima Y, Suzuki O, Nakagawa S, Senoh A, Mizoguchi H, Goto Y, Shimizu F, Wakebe H, Hishigaki H, Watanabe T, Sugiyama A, Takemoto M, Kawakami B, Yamazaki M, Watanabe K, Kumagai A, Itakura S, Fukuzumi Y, Fujimori Y, Komiyama M, Tashiro H, Tanigami A, Fujiwara T, Ono T, Yamada K, Fujii Y, Ozaki K, Hirao M, Ohmori Y, Kawabata A, Hikiji T, Kobatake N, Inagaki H, Ikema Y, Okamoto S, Okitani R, Kawakami T, Noguchi S, Itoh T, Shigeta K, Senba T, Matsumura K, Nakajima Y, Mizuno T, Morinaga M, Sasaki M, Togashi T, Oyama M, Hata H, Watanabe M, Komatsu T, Mizushima-Sugano J, Satoh T, Shirai Y, Takahashi Y, Nakagawa K, Okumura K, Nagase T, Nomura N, Kikuchi H, Masuho Y, Yamashita R, Nakai K, Yada T, Nakamura Y, Ohara O, Isogai T, Sugano S: Complete sequencing and characterization of 21,243 full-length human cDNAs. Nat Genet. 2004 Jan;36(1):40-5. doi: 10.1038/ng1285. Epub 2003 Dec 21.
Pubmed: 14702039
Leung S, Qureshi SA, Kerr IM, Darnell JE Jr, Stark GR: Role of STAT2 in the alpha interferon signaling pathway. Mol Cell Biol. 1995 Mar;15(3):1312-7. doi: 10.1128/mcb.15.3.1312.
Pubmed: 7532278
Li X, Leung S, Kerr IM, Stark GR: Functional subdomains of STAT2 required for preassociation with the alpha interferon receptor and for signaling. Mol Cell Biol. 1997 Apr;17(4):2048-56. doi: 10.1128/mcb.17.4.2048.
Pubmed: 9121453
Precious B, Childs K, Fitzpatrick-Swallow V, Goodbourn S, Randall RE: Simian virus 5 V protein acts as an adaptor, linking DDB1 to STAT2, to facilitate the ubiquitination of STAT1. J Virol. 2005 Nov;79(21):13434-41. doi: 10.1128/JVI.79.21.13434-13441.2005.
Pubmed: 16227264
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