title: The CATS (FAM64A) protein is a substrate of the Kinase Interacting Stathmin (KIS).
abstract: The CATS protein (also known as FAM64A and RCS1) was first identified as a novel CALM (PICALM) interactor that influences the subcellular localization of the leukemogenic fusion protein CALM/AF10. CATS is highly expressed in cancer cell lines in a cell cycle dependent manner and is induced by mitogens. CATS is considered a marker for proliferation, known to control the metaphase-to-anaphase transition during the cell division. Using CATS as a bait in a yeast two-hybrid screen we identified the Kinase Interacting Stathmin (KIS or UHMK1) protein as a CATS interacting partner. The interaction between CATS and KIS was confirmed by GST pull-down, co-immunoprecipitation and co-localization experiments. Using kinase assay we showed that CATS is a substrate of KIS and mapped the phosphorylation site to CATS serine 131 (S131). Protein expression analysis revealed that KIS levels changed in a cell cycle-dependent manner and in the opposite direction to CATS levels. In a reporter gene assay KIS was able to enhance the transcriptional repressor activity of CATS, independent of CATS phophorylation at S131. Moreover, we showed that CATS and KIS antagonize the transactivation capacity of CALM/AF10.In summary, our results show that CATS interacts with and is a substrate for KIS, suggesting that KIS regulates CATS function.
authors: Hematology and Hemotherapy Center, State University of Campinas, Campinas, Brazil. leticiaf@unicamp.br
authors: Leticia Fröhlich
authors: LF
authors: Archangelo
authors: Philipp A
authors: PA
authors: Greif
authors: Alexandre
authors: A
authors: Maucuer
authors: Valérie
authors: V
authors: Manceau
authors: Naresh
authors: N
authors: Koneru
authors: Carolina L
authors: CL
authors: Bigarella
authors: Fernanda
authors: F
authors: Niemann
authors: Marcos Tadeu
authors: MT
authors: dos Santos
authors: Jörg
authors: J
authors: Kobarg
authors: Stefan K
authors: SK
authors: Bohlander
authors: Sara Teresinha Olalla
authors: ST
authors: Saad
mesh_terms: D001665:Binding Sites; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism; D015972:Gene Expression Regulation, Neoplastic; D057809:HEK293 Cells; D006801:Humans; D047468:Immunoprecipitation; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics / Q000378:metabolism; D009687:Nuclear Proteins; D015514:Oncogene Proteins, Fusion / Q000235:genetics / Q000378:metabolism; D010766:Phosphorylation; D011485:Protein Binding; D060066:Protein Interaction Maps; D017346:Protein Serine-Threonine Kinases / Q000235:genetics / Q000378:metabolism
chemical_list: C114359:AF10-CALM fusion protein, human; D002352:Carrier Proteins; D047908:Intracellular Signaling Peptides and Proteins; D009687:Nuclear Proteins; D015514:Oncogene Proteins, Fusion; C512398:PIMREG protein, human; D017346:Protein Serine-Threonine Kinases; C530658:UHMK1 protein, human