Abstract
MARP Protein Family: A Possible Role in Molecular Mechanisms of TumorigenesisThe MARP (muscle ankyrin repeat protein) family comprises three structurally similar proteins: CARP/Ankrd1, Ankrd2/Arpp and DARP/Ankrd23. They share four conserved copies of 33-residue ankyrin repeats and contain a nuclear localization signal, allowing the sorting of MARPs to the nucleus. They are found both in the nucleus and in the cytoplasm of skeletal and cardiac muscle cells, suggesting that MARPs shuttle within the cell enabling them to play a role in signal transduction in striated muscle. Expression of MARPs is altered under different pathological conditions. In skeletal muscle, CARP/Ankrd1 and Ankrd2/Arpp are up-regulated in muscle in patients suffering from Duchene muscular dystrophy, congenital myopathy and spinal muscular atrophy. Mutations inAnkrd1gene (coding CARP/Ankrd1) were identified in dilated and hypertrophic cardiomyopathies. Altered expression of MARPs is also observed in rhabdomyosarcoma, renal oncocytoma and ovarian cancer. In order to functionally characterize MARP family members CARP/Ankrd1 and Ankrd2/Arpp, we have found that both proteins interact with the tumor suppressor p53 bothin vivoandin vitroand that p53 up-regulates their expression. Our results implicate the potential role of MARPs in molecular mechanisms relevant to tumor response and progression.
Highlights
Cardiac ankyrin repeat protein (CARP/Ankrd1) and ankyrin repeat domain 2 (Ankrd2/Arpp), together with diabetes associated ankyrin repeat protein (DARP), belong to a conserved muscle ankyrin repeat protein (MARP) family [1]
Summary: The MARP family comprises three structurally similar proteins: CARP/Ankrd1, Ankyrin repeat domain 2 (Ankrd2)/Arpp and DARP/Ankrd23. They share four conserved copies of 33-residue ankyrin repeats and contain a nuclear localization signal, allowing the sorting of MARPs to the nucleus. They are found both in the nucleus and in the cytoplasm of skeletal and cardiac muscle cells, suggesting that MARPs shuttle within the cell enabling them to play a role in signal transduction in striated muscle
Expression of MARPs is altered under different pathological conditions
Summary
Cardiac ankyrin repeat protein (CARP/Ankrd1) and ankyrin repeat domain 2 (Ankrd2/Arpp), together with diabetes associated ankyrin repeat protein (DARP), belong to a conserved muscle ankyrin repeat protein (MARP) family [1]. CARP/Ankrd has been independently identified by several groups as a cytokine-inducible transcriptional regulator, a protein interacting with transcriptional factor YB-1, and a cardiac doxorubicin-responsive protein [3,4,5] In normal tissues, it is highly expressed in cardiac muscle and detectable in skeletal muscles [4]. Apart from transcription factors, Ankrd2/Arpp interacts with the sarcomeric proteins telethonin [20] and titin [1], suggesting that it may translocate from the I band to the nucleus and participate in signaling pathways activated in response to muscle stress Protein–protein interactions with functionally diverse proteins and the dual nuclear-cytoplasmic localization of CARP/Ankrd and Ankrd2/Arpp point to their structural and regulatory functions as components of a titin associated stretch-sensing complex in the myofibril and as co-factors of transcription in the nucleus. These results indicate that CARP/Ankrd and Ankrd2/Arpp may have a potential use in the diagnostics of RMS
Sign-in/Register to view highlights & summary 
Published Version (
Free)
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
