title: CIP2A inhibits PP2A in human malignancies.
abstract: Inhibition of protein phosphatase 2A (PP2A) activity has been identified as a prerequisite for the transformation of human cells. However, the molecular mechanisms by which PP2A activity is inhibited in human cancers are currently unclear. In this study, we describe a cellular inhibitor of PP2A with oncogenic activity. The protein, designated Cancerous Inhibitor of PP2A (CIP2A), interacts directly with the oncogenic transcription factor c-Myc, inhibits PP2A activity toward c-Myc serine 62 (S62), and thereby prevents c-Myc proteolytic degradation. In addition to its function in c-Myc stabilization, CIP2A promotes anchorage-independent cell growth and in vivo tumor formation. The oncogenic activity of CIP2A is demonstrated by transformation of human cells by overexpression of CIP2A. Importantly, CIP2A is overexpressed in two common human malignancies, head and neck squamous cell carcinoma (HNSCC) and colon cancer. Thus, our data show that CIP2A is a human oncoprotein that inhibits PP2A and stabilizes c-Myc in human malignancies.
authors.affiliation: Centre for Biotechnology, University of Turku and Abo Akademi University, 20520 Turku, Finland.
authors.forename: Melissa R
authors.initials: MR
authors.lastname: Junttila
authors.forename: Pietri
authors.initials: P
authors.lastname: Puustinen
authors.forename: Minna
authors.initials: M
authors.lastname: Niemelä
authors.forename: Raija
authors.initials: R
authors.lastname: Ahola
authors.forename: Hugh
authors.initials: H
authors.lastname: Arnold
authors.forename: Trine
authors.initials: T
authors.lastname: Böttzauw
authors.forename: Risto
authors.initials: R
authors.lastname: Ala-aho
authors.forename: Christina
authors.initials: C
authors.lastname: Nielsen
authors.forename: Johanna
authors.initials: J
authors.lastname: Ivaska
authors.forename: Yoichi
authors.initials: Y
authors.lastname: Taya
authors.forename: Shi-Long
authors.initials: SL
authors.lastname: Lu
authors.forename: Shujun
authors.initials: S
authors.lastname: Lin
authors.forename: Edward K L
authors.initials: EK
authors.lastname: Chan
authors.forename: Xiao-Jing
authors.initials: XJ
authors.lastname: Wang
authors.forename: Reidar
authors.initials: R
authors.lastname: Grènman
authors.forename: Juergen
authors.initials: J
authors.lastname: Kast
authors.forename: Tuula
authors.initials: T
authors.lastname: Kallunki
authors.forename: Rosalie
authors.initials: R
authors.lastname: Sears
authors.forename: Veli-Matti
authors.initials: VM
authors.lastname: Kähäri
authors.forename: Jukka
authors.initials: J
authors.lastname: Westermarck
mesh_terms: D000818:Animals; D001324:Autoantigens / Q000235:genetics / Q000378:metabolism*; D002294:Carcinoma, Squamous Cell / Q000235:genetics / Q000378:metabolism*; D002460:Cell Line; D002471:Cell Transformation, Neoplastic; D003110:Colonic Neoplasms / Q000235:genetics / Q000378:metabolism*; D004791:Enzyme Inhibitors / Q000378:metabolism*; D006258:Head and Neck Neoplasms / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism*; D054648:Protein Phosphatase 2 / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism; D016271:Proto-Oncogene Proteins c-myc / Q000235:genetics / Q000378:metabolism*; D034741:RNA, Small Interfering / Q000235:genetics / Q000378:metabolism
chemical_list: D001324:Autoantigens; C500266:CIP2A protein, human; D004791:Enzyme Inhibitors; D047908:Intracellular Signaling Peptides and Proteins; D008565:Membrane Proteins; D016271:Proto-Oncogene Proteins c-myc; D034741:RNA, Small Interfering; D054648:Protein Phosphatase 2