The novel CALM interactor CATS influences the subcellular localization of the leukemogenic fusion protein CALM/AF10.
The Clathrin Assembly Lymphoid Myeloid leukemia gene (CALM or PICALM) was first identified as the fusion partner of AF10 in the t(10;11)(p13;q14) translocation, which is observed in acute myeloid leukemia (AML), acute lymphoblastic leukemia (ALL) and malignant lymphoma. The CALM/AF10 fusion protein plays a crucial role in t(10;11)(p13;q14) associated leukemogenesis. Using the N-terminal half of CALM as a bait in a yeast two-hybrid screen, a novel protein named CATS (CALM interacting protein expressed in thymus and spleen) was identified. Multiple tissue Northern blot analysis showed predominant expression of CATS in thymus, spleen and colon. CATS codes for two protein isoforms of 238 and 248 amino acids (aa). The interaction between CALM and CATS could be confirmed using pull down assays, co-immunoprecipitation and colocalization experiments. The CATS interaction domain of CALM was mapped to aa 221-335 of CALM. This domain is contained in the CALM/AF10 fusion protein. CATS localizes to the nucleus and shows a preference for nucleoli. Expression of CATS was able to markedly increase the nuclear localization of CALM and of the leukemogenic fusion protein CALM/AF10. The possible implications of these findings for CALM/AF10-mediated leukemogenesis are discussed.
Department of Medicine III, University of Munich Hospital Grosshadern, Marchioninistr, Munich, Germany.
L Fröhlich
LF
Archangelo
J
J
Gläsner
A
A
Krause
S K
SK
Bohlander
D016475:3T3 Cells; D021581:Active Transport, Cell Nucleus / Q000235:genetics; D000818:Animals; D001483:Base Sequence; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism*; D002466:Cell Nucleolus / Q000235:genetics / Q000378:metabolism*; D002471:Cell Transformation, Neoplastic / Q000235:genetics; D002879:Chromosomes, Human, Pair 10 / Q000235:genetics / Q000378:metabolism; D002882:Chromosomes, Human, Pair 13 / Q000235:genetics / Q000378:metabolism; D005786:Gene Expression Regulation / Q000235:genetics; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins; D051379:Mice; D008969:Molecular Sequence Data; D034041:Monomeric Clathrin Assembly Proteins / Q000235:genetics / Q000378:metabolism*; D009687:Nuclear Proteins; D015514:Oncogene Proteins, Fusion / Q000235:genetics / Q000378:metabolism*; D009928:Organ Specificity; D011485:Protein Binding / Q000235:genetics; D014178:Translocation, Genetic / Q000235:genetics
C114359:AF10-CALM fusion protein, human; D002352:Carrier Proteins; D047908:Intracellular Signaling Peptides and Proteins; D034041:Monomeric Clathrin Assembly Proteins; D009687:Nuclear Proteins; D015514:Oncogene Proteins, Fusion; C439003:PICALM protein, human; C512398:PIMREG protein, human