Online citations, reference lists, and bibliographies.
← Back to Search

The EF-hand Calcium-binding Protein Calmyrin Inhibits The Transcriptional And DNA-binding Activity Of Pax3.

A. Hollenbach, C. J. McPherson, I. Lagutina, G. Grosveld
Published 2002 · Medicine, Biology

Cite This
Download PDF
Analyze on Scholarcy
Pax3 is a member of the paired class homeodomain family of transcription factors and has been demonstrated to be an early marker in myogenic differentiation. To gain a better understanding of how protein-protein interactions regulate Pax3 transcriptional activity, we performed a yeast two-hybrid analysis to identify proteins that interact with Pax3. Screening of two cDNA libraries isolated nine independent clones that contained the complete encoding sequence of the EF-hand calcium-binding protein calmyrin. In this report, we demonstrate that calmyrin specifically interacts with Pax3 in vitro. In addition, we demonstrate that the interaction between Pax3 and calmyrin is mediated by the region of the Pax3 paired domain that is involved in making DNA contacts and the Pax3 octapeptide domain and its surrounding amino acid sequences. We also demonstrate that endogenous Pax3 and calmyrin are co-expressed in undifferentiated primary myoblasts and that calmyrin expression levels increase in the nucleus upon myogenic differentiation. Finally, we demonstrate that co-expression of calmyrin with Pax3 inhibits the transcriptional activity of Pax3 by inhibiting Pax3 from binding to its recognition DNA sequences. These results therefore suggest potential ways in which calcium, through its regulation of the EF-hand calcium-binding protein calmyrin, can alter the DNA-binding activity and subsequent transcriptional activity of Pax3.
This paper references
Calcium/calmodulin inhibition of basic-helix-loop-helix transcription factor domains
B. Corneliussen (1994)
Interactions of myogenic bHLH transcription factors with calcium-binding calmodulin and S100a (alpha alpha) proteins.
J. Baudier (1995)
Molecular mechanics of calcium–myristoyl switches
J. Ames (1997)
Interaction of the pRB-family proteins with factors containing paired-like homeodomains
O. Wiggan (1998)
Regulation of Pax-3 expression in the dermomyotome and its role in muscle development.
M. Goulding (1994)
Crystal structure of a paired domain-DNA complex at 2.5 å resolution reveals structural basis for pax developmental mutations
W. Xu (1995)
The Oncogenic Potential of the Pax3-FKHR Fusion Protein Requires the Pax3 Homeodomain Recognition Helix but Not the Pax3 Paired-Box DNA Binding Domain
P. Y. Lam (1999)
Structures of the platelet calcium‐ and integrin‐binding protein and the αIIb‐integrin cytoplasmic domain suggest a mechanism for calcium‐regulated recognition; homology modelling and NMR studies
P. Hwang (2000)
Divalent Cations Differentially Regulate Integrin αIIb Cytoplasmic Tail Binding to β3 and to Calcium- and Integrin-binding Protein*
L. Vallar (1999)
The DNA binding activity of the paired box transcription factor Pax‐3 is rapidly downregulated during neuronal cell differentiation
F. Reeves (1998)
Pax-3 expression in segmental mesoderm marks early stages in myogenic cell specification.
B. Williams (1994)
Cdi1, a human G1 and S phase protein phosphatase that associates with Cdk2
J. Gyuris (1993)
The differentiation of chick embryonic skin. An electron microscopic study with a description of a peculiar epidermal cytoplasmic ultrastructure.
N. Mottet (1968)
Wild type PAX3 protein and the PAX3-FKHR fusion protein of alveolar rhabdomyosarcoma contain potent, structurally distinct transcriptional activation domains.
J. Bennicelli (1995)
Ectopic Pax-3 Activates MyoD and Myf-5 Expression in Embryonic Mesoderm and Neural Tissue
M. Maroto (1997)
Changes in the mechanism of Ca2(+) mobilization during the differentiation of BC3H1 muscle cells.
H. de Smedt (1991)
Fate restriction in limb muscle precursor cells precedes high-level expression of MyoD family member genes.
B. Williams (2000)
The EF-hand family of calcium-modulated proteins
A. Persechini (1989)
Pax-3 is required for the development of limb muscles: a possible role for the migration of dermomyotomal muscle progenitor cells.
E. Bober (1994)
A Myristoylated Calcium-binding Protein that Preferentially Interacts with the Alzheimer's Disease Presenilin 2 Protein
Stacy M. Stabler (1999)
HIRA, a mammalian homologue of Saccharomyces cerevisiae transcriptional co-repressors, interacts with Pax3
P. Magnaghi (1998)
Evolution of the EF-hand family of proteins.
S. Nakayama (1994)
Identification of a Novel Calcium-binding Protein That Interacts with the Integrin αIIb Cytoplasmic Domain*
U. Naik (1997)
Identification of the immunophilins capable of mediating inhibition of signal transduction by cyclosporin A and FK506: roles of calcineurin binding and cellular location.
R. Bram (1993)
High resolution crystal structure of a paired (Pax) class cooperative homeodomain dimer on DNA
D. B. Wilson (1995)
Redefining the Genetic Hierarchies Controlling Skeletal Myogenesis: Pax-3 and Myf-5 Act Upstream of MyoD
S. Tajbakhsh (1997)

This paper is referenced by
Structural and Biochemical Characterization of CIB1 Delineates a New Family of EF-hand-containing Proteins*
Holly R Gentry (2005)
Ozz-E3 Ubiquitin Ligase Targets Sarcomeric Embryonic Myosin Heavy Chain during Muscle Development
Y. Campos (2010)
CIB1 and CaBP1 bind to the myo1c regulatory domain
N. Tang (2007)
Tickling the tails: cytoplasmic domain proteins that regulate integrin αIIbβ3 activation
T. M. Leisner (2007)
Ozz-E3, a muscle-specific ubiquitin ligase, regulates beta-catenin degradation during myogenesis.
Tommaso Nastasi (2004)
CIB1 Mediated Regulation of Endothelial Cells and Pathological Angiogenesis
M. A. Zayed (2007)
Tumor growth and angiogenesis is impaired in CIB1 knockout mice
M. A. Zayed (2010)
Identification and characterization of PKD2 substrates - CIB1A as a substrate for PKD2
M. Armacki (2010)
Calcium-binding calmyrin forms stable covalent dimers in vitro, but in vivo is found in monomeric form.
A. Sobczak (2005)
CIB1 Synergizes with EphrinA2 to Regulate Kaposi's Sarcoma-Associated Herpesvirus Macropinocytic Entry in Human Microvascular Dermal Endothelial Cells
Chirosree Bandyopadhyay (2014)
Calcium‐ and magnesium‐dependent interactions between calcium‐ and integrin‐binding protein and the integrin αIIb cytoplasmic domain
Aaron P. Yamniuk (2005)
Edd, the Murine Hyperplastic Disc Gene, Is Essential for Yolk Sac Vascularization and Chorioallantoic Fusion
D. Saunders (2004)
Notch signaling via Hes1 transcription factor maintains survival of melanoblasts and melanocyte stem cells
M. Moriyama (2006)
Translocation of Sphingosine Kinase 1 to the Plasma Membrane Is Mediated by Calcium- and Integrin-binding Protein 1*
Kate E. Jarman (2009)
Role of the Sodium–calcium Exchanger (NCX‐1) within Splotch (Sp2h) Myocardial Failure
J. Wang (2007)
Identification of serine 205 as a site of phosphorylation on Pax3 in proliferating but not differentiating primary myoblasts
P. J. Miller (2008)
The Emerging Roles of CIB1 in Cancer
X. Wang (2017)
Profiling of Autoantibodies in Sera of Pancreatic Cancer Patients
Y. Nagayoshi (2014)
The oncogenic fusion protein Pax3-FKHR has a greater post-translational stability relative to Pax3 during early myogenesis.
P. J. Miller (2007)
Role of transcription factors in skeletal muscle and the potential for pharmacological manipulation.
P. T. Martin (2003)
CIB1 and CIB2 are HIV-1 helper factors involved in viral entry
Ana Godinho-Santos (2016)
Calcium binding sequences in calmyrin regulates interaction with presenilin-2.
Jingsong Zhu (2004)
Discovery and Characterization of Peptide Inhibitors for Calcium and Integrin Binding Protein 1.
A. C. Puhl (2020)
Calmyrin1 binds to SCG10 protein (stathmin2) to modulate neurite outgrowth.
A. Sobczak (2011)
Alternative splicing of Pax3 produces a transcriptionally inactive protein.
C. Pritchard (2003)
Pigmentation PAX‐ways: the role of Pax3 in melanogenesis, melanocyte stem cell maintenance, and disease
Jennifer D. Kubic (2008)
A novel splice variant of calcium and integrin-binding protein 1 mediates protein kinase D2-stimulated tumour growth by regulating angiogenesis
M. Armacki (2014)
The role of Pax genes in the development of tissues and organs: Pax3 and Pax7 regulate muscle progenitor cell functions.
M. Buckingham (2007)
The expression and function of PAX3 in development and disease.
S. Boudjadi (2018)
Alternative splicing and tissue expression of CIB4 gene in sheep testis.
Yan Yu (2010)
PAX3 and PAX7 as upstream regulators of myogenesis.
M. Buckingham (2015)
CIB1: a small protein with big ambitions
T. M. Leisner (2016)
See more
Semantic Scholar Logo Some data provided by SemanticScholar