title: The Ankrd2 protein, a link between the sarcomere and the nucleus in skeletal muscle.
abstract: Ankrd2 may be a link between the sarcomere and the nucleus; a similar role has recently been proposed for CARP that has a high level of structural and functional conservation with Ankrd2. Both Ankrd2 and CARP are involved in striated muscle hypertrophy. The mechanism by which muscle stretch is sensed and signals are transduced is still unknown; however, Ankrd2 and CARP could play similar roles in pathways leading to hypertrophy, the triggering mechanisms being heart pressure overload monitored by CARP and mechanical stretch in skeletal muscle monitored by Ankrd2. Recently Ankrd2 and CARP have been proposed as members of a family of muscle ankyrin repeat proteins (MARPs) that form a complex with titin, myopalladin and calpain protease p94, involved in signaling and regulation of gene expression in response to muscle stress. Here, we show that Ankrd2 is able to interact with the Z-disc protein telethonin as well as being able to interact with three transcription factors: YB-1, PML and p53. Ankrd2 binding to the ubiquitous transcription factor YB-1 can be demonstrated both in vitro and in vivo; this is not very surprising, since a similar interaction was previously described for CARP. However, the interactions with PML and p53 are unexpected new findings, with interesting implications in the Ankrd2 signaling cascade. Ankrd2 co-localizes with the transcriptional co-activator and co-repressor PML in nuclear bodies (NBs) in human myoblasts as detected by confocal immunofluorescence. Interestingly, we show that Ankrd2 not only binds the tumor suppressor protein p53 both in vitro and in vivo but also enhances the up-regulation of the p21(WAFI/CIPI) promoter by p53. Therefore, our findings strengthen the hypothesis that Ankrd2 may be involved in sensing stress signals and linking these to muscle gene regulation.
authors.affiliation: International Centre for Genetic Engineering and Biotechnology, Padriciano 99, I-34012 Trieste, Italy.
authors.forename: Snezana
authors.initials: S
authors.lastname: Kojic
authors.forename: Elisa
authors.initials: E
authors.lastname: Medeot
authors.forename: Ernesto
authors.initials: E
authors.lastname: Guccione
authors.forename: Helena
authors.initials: H
authors.lastname: Krmac
authors.forename: Ivano
authors.initials: I
authors.lastname: Zara
authors.forename: Valentina
authors.initials: V
authors.lastname: Martinelli
authors.forename: Giorgio
authors.initials: G
authors.lastname: Valle
authors.forename: Georgine
authors.initials: G
authors.lastname: Faulkner
mesh_terms: D022762:CCAAT-Enhancer-Binding Proteins / Q000378:metabolism; D002467:Cell Nucleus / Q000378:metabolism*; D002478:Cells, Cultured; D064211:Connectin; D050759:Cyclin-Dependent Kinase Inhibitor p21; D016213:Cyclins / Q000235:genetics / Q000378:metabolism; D006801:Humans; D008856:Microscopy, Fluorescence; D009124:Muscle Proteins / Q000378:metabolism*; D018482:Muscle, Skeletal / Q000378:metabolism*; D051839:NFI Transcription Factors; D009363:Neoplasm Proteins / Q000378:metabolism; D009687:Nuclear Proteins / Q000378:metabolism; D011401:Promoter Regions, Genetic; D000071156:Promyelocytic Leukemia Protein; D011485:Protein Binding; D012097:Repressor Proteins / Q000378:metabolism; D012518:Sarcomeres / Q000378:metabolism*; D014157:Transcription Factors / Q000378:metabolism; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism; D025521:Tumor Suppressor Proteins; D015854:Up-Regulation; D051840:Y-Box-Binding Protein 1
chemical_list: C491304:ANKRD1 protein, human; C432364:ANKRD2 protein, human; C485877:Ankrd2 protein, mouse; D022762:CCAAT-Enhancer-Binding Proteins; C493956:CDKN1A protein, human; D064211:Connectin; D050759:Cyclin-Dependent Kinase Inhibitor p21; D016213:Cyclins; D009124:Muscle Proteins; D051839:NFI Transcription Factors; D009363:Neoplasm Proteins; D009687:Nuclear Proteins; C513293:Pml protein, mouse; D000071156:Promyelocytic Leukemia Protein; D012097:Repressor Proteins; C577292:TCAP protein, human; D014157:Transcription Factors; D016159:Tumor Suppressor Protein p53; D025521:Tumor Suppressor Proteins; D051840:Y-Box-Binding Protein 1; C070576:PML protein, human