The Ankrd2 protein, a link between the sarcomere and the nucleus in skeletal muscle

Snezana Kojic, Elisa Medeot, Ernesto Guccione, Helena Krmac, Ivano Zara, Valentina Martinelli, Giorgio Valle, Georgine Faulkner

Research output: Contribution to journalArticlepeer-review

118 Scopus citations


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 p21WAFI/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.

Original languageEnglish
Pages (from-to)313-325
Number of pages13
JournalJournal of Molecular Biology
Issue number2
StatePublished - 28 May 2004
Externally publishedYes


  • Ankrd2/Arpp and CARP
  • Co-IP, co-immunoprecipitation
  • GST, glutathione-S-transferase
  • IP, immunoprecipitation
  • IVTT, in vitro transcripted and translated
  • PML
  • Wb, Western blot
  • YB-1
  • aa, amino acid
  • muscle ankyrin repeat proteins
  • p53


Dive into the research topics of 'The Ankrd2 protein, a link between the sarcomere and the nucleus in skeletal muscle'. Together they form a unique fingerprint.

Cite this