Identification and characterization of a nuclear interacting partner of anaplastic lymphoma kinase (NIPA)

Tao Ouyang, Renyuan Bai, Florian Bassermann, Christine Von Klitzing, Silvia Klumpen, Cornelius Miething, Stephan W. Morris, Christian Peschel, Justus Duyster

Research output: Contribution to journalArticle

Abstract

Anaplastic large-cell lymphoma is a subtype of non-Hodgkin lymphomas characterized by the expression of CD30. More than half of these lymphomas carry a chromosomal translocation t(2;5) leading to expression of the oncogenic tyrosine kinase nucleophosmin-anaplastic lymphoma kinase (NPM-ALK). NPM-ALK is capable of transforming fibroblasts and lymphocytes in vitro and of causing lymphomas in mice. Previously, we and others demonstrated phospholipase C-γ and phosphatidylinositol 3-kinase as crucial downstream signaling mediators of NPM-ALK-induced oncogenicity. In this study, we used an ALK fusion protein as bait in a yeast two-hybrid screen identifying NIPA (nuclear interacting partner of ALK) as a novel downstream target of NPM-ALK. NIPA encodes a 60-kDa protein that is expressed in a broad range of human tissues and contains a classical nuclear translocation signal in its C terminus, which directs its nuclear localization. NIPA interacts with NPM-ALK and other ALK fusions in a tyrosine kinase-dependent manner and is phosphorylated in NPM-ALK-expressing cells on tyrosine and serine residues with serine 354 as a major phosphorylation site. Overexpression of NIPA in Ba/F3 cells was able to protect from apoptosis induced by IL-3 withdrawal. Mutations of the nuclear translocation signal or the Ser-354 phosphorylation site impaired the antiapoptotic function of NIPA. In NPM-ALK-transformed Ba/F3 cells, apoptosis triggered by wortmannin treatment was enhanced by overexpression of putative dominant-negative NIPA mutants. These results implicate an antiapoptotic role for NIPA in NPM-ALK-mediated signaling events.

Original languageEnglish (US)
Pages (from-to)30028-30036
Number of pages9
JournalJournal of Biological Chemistry
Volume278
Issue number32
DOIs
StatePublished - Aug 8 2003
Externally publishedYes

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Phosphorylation
anaplastic lymphoma kinase
Protein-Tyrosine Kinases
Serine
Lymphoma
Fusion reactions
Phosphatidylinositol 3-Kinase
Apoptosis
Anaplastic Large-Cell Lymphoma
Genetic Translocation
Lymphocytes
nucleophosmin
Interleukin-3
Type C Phospholipases
Fibroblasts
Yeast
Non-Hodgkin's Lymphoma
Tyrosine
Proteins
Yeasts

ASJC Scopus subject areas

  • Biochemistry

Cite this

Ouyang, T., Bai, R., Bassermann, F., Von Klitzing, C., Klumpen, S., Miething, C., ... Duyster, J. (2003). Identification and characterization of a nuclear interacting partner of anaplastic lymphoma kinase (NIPA). Journal of Biological Chemistry, 278(32), 30028-30036. https://doi.org/10.1074/jbc.M300883200

Identification and characterization of a nuclear interacting partner of anaplastic lymphoma kinase (NIPA). / Ouyang, Tao; Bai, Renyuan; Bassermann, Florian; Von Klitzing, Christine; Klumpen, Silvia; Miething, Cornelius; Morris, Stephan W.; Peschel, Christian; Duyster, Justus.

In: Journal of Biological Chemistry, Vol. 278, No. 32, 08.08.2003, p. 30028-30036.

Research output: Contribution to journalArticle

Ouyang, T, Bai, R, Bassermann, F, Von Klitzing, C, Klumpen, S, Miething, C, Morris, SW, Peschel, C & Duyster, J 2003, 'Identification and characterization of a nuclear interacting partner of anaplastic lymphoma kinase (NIPA)', Journal of Biological Chemistry, vol. 278, no. 32, pp. 30028-30036. https://doi.org/10.1074/jbc.M300883200
Ouyang, Tao ; Bai, Renyuan ; Bassermann, Florian ; Von Klitzing, Christine ; Klumpen, Silvia ; Miething, Cornelius ; Morris, Stephan W. ; Peschel, Christian ; Duyster, Justus. / Identification and characterization of a nuclear interacting partner of anaplastic lymphoma kinase (NIPA). In: Journal of Biological Chemistry. 2003 ; Vol. 278, No. 32. pp. 30028-30036.
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