ALK-, STAT3- and MECP2-dependent STAT5A gene repression

Stable Identifier
Reaction [BlackBoxEvent]
Homo sapiens
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STAT5A is expressed in NPM-ALK T-cell lymphomas in a manner that depends on STAT3 and MeCP2. STAT3 activation downstream of NPM-ALK stimulates STAT5A promoter hypermethylation, providing binding sites for MeCP2 and resulting in the repression of STAT5 expression (Zhang et al, 2007; Zhang et al, 2002). In turn, STAT5 has been shown to have binding sites at two places in the NPM-ALK fusion gene: an enhancer element located upstream of the endogenous NPM gene, and in intron 14 of the ALK gene. STAT5A has been shown to bind to these elements by electrophoretic mobility shift assay (EMSA) and by co-immunoprecipitation (Zhang et al, 2007).

Literature References
PubMed ID Title Journal Year
17922009 STAT5A is epigenetically silenced by the tyrosine kinase NPM1-ALK and acts as a tumor suppressor by reciprocally inhibiting NPM1-ALK expression

Liu, X, Wasik, MA, Zhang, Q, Wang, HY

Nat. Med. 2007
11751994 Multilevel dysregulation of STAT3 activation in anaplastic lymphoma kinase-positive T/null-cell lymphoma

Wasik, MA, Zhang, Q, Carpentieri, DF, Morris, S, Odum, N, Skorski, T, Raghunath, PN, Majewski, M, Xue, L

J. Immunol. 2002
This event is regulated
Name Identifier Synonyms
cancer DOID:162 malignant tumor, malignant neoplasm, primary cancer
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