title: The tumor suppressor hTid1 inhibits STAT5b activity via functional interaction.
abstract: STAT5a and -5b (signal transducers and activators of transcription 5a and 5b) proteins play an essential role in hematopoietic cell proliferation and survival and are frequently constitutively active in hematologic neoplasms and solid tumors. Because STAT5a and STAT5b differ mainly in the carboxyl-terminal transactivation domain, we sought to identify new proteins that bind specifically to this domain by using a bacterial two-hybrid screening. We isolated hTid1, a human DnaJ protein that acts as a tumor suppressor in various solid tumors. hTid1 interacts specifically with STAT5b but not with STAT5a in hematopoietic cell lines. This interaction involves the cysteine-rich region of the hTid1 DnaJ domain. We also demonstrated that hTid1 negatively regulates the expression and transcriptional activity of STAT5b and suppresses the growth of hematopoietic cells transformed by an oncogenic form of STAT5b. Our findings define hTid1 as a novel partner and negative regulator of STAT5b.
authors.affiliation: INSERM, U925, Université de Picardie Jules Verne, UFR de Médecine, 3 Rue des Louvels, 80036 Amiens, France.
authors.forename: Isabelle
authors.initials: I
authors.lastname: Dhennin-Duthille
authors.forename: Rémy
authors.initials: R
authors.lastname: Nyga
authors.forename: Saliha
authors.initials: S
authors.lastname: Yahiaoui
authors.forename: Valérie
authors.initials: V
authors.lastname: Gouilleux-Gruart
authors.forename: Aline
authors.initials: A
authors.lastname: Régnier
authors.forename: Kaïss
authors.initials: K
authors.lastname: Lassoued
authors.forename: Fabrice
authors.initials: F
authors.lastname: Gouilleux
mesh_terms: D000818:Animals; D019556:COS Cells; D002471:Cell Transformation, Neoplastic / Q000235:genetics / Q000378:metabolism; D002522:Chlorocebus aethiops; D050956:HSP40 Heat-Shock Proteins / Q000235:genetics / Q000378:metabolism*; D006412:Hematopoietic Stem Cells / Q000378:metabolism; D006801:Humans; D019169:Jurkat Cells; D051379:Mice; D017434:Protein Structure, Tertiary; D050799:STAT5 Transcription Factor / Q000235:genetics / Q000378:metabolism*; D025521:Tumor Suppressor Proteins / Q000235:genetics / Q000378:metabolism
chemical_list: C120664:DNAJA3 protein, human; C485636:Dnaja3 protein, mouse; D050956:HSP40 Heat-Shock Proteins; D050799:STAT5 Transcription Factor; C494092:STAT5A protein, human; C494095:STAT5B protein, human; C494093:Stat5a protein, mouse; C494096:Stat5b protein, mouse; D025521:Tumor Suppressor Proteins