Disease relevance of SYNPO2

• Myopodin was reported as a gene frequently deleted in prostate cancer [1].
• Expression of myopodin induces suppression of tumor growth and metastasis [1].

High impact information on SYNPO2

• Nuclear export of myopodin is sensitive to leptomycin B, despite the absence of a classical nuclear export sequence [2].
• During myotube differentiation, myopodin binds to stress fibers in a punctuated pattern before incorporation into the Z-disc [2].
• Myopodin can directly bind to actin and contains a novel actin binding site in the center of the protein [2].
• Myopodin has actin-bundling activity as shown by formation of latrunculin-A-sensitive cytosolic actin bundles, nuclear actin loops in transfected cells expressing green fluorescent protein-myopodin [2] and electron microscopy [3].
• In myoblasts, myopodin shows preferential nuclear localization [2].
• Myopodin is a multiadapter protein interacting with (in addition to F-actin) filamin and alpha-actinin [4].
• Myopodin is a key component in filamin homeostasis by mediating interactions with the cochaperone BAG3 and Vps18  [5].

Biological context of SYNPO2

• Myopodin is a key component in tension-induced and chaperone-assisted autophagy
• Results from non-muscle cells support the hypothesis that myopodin functions as a tumor suppressor gene to limit the growth and to inhibit the metastasis of cancer cells [1].
• In addition, hemizygous deletion and down-regulation of myopodin expression occur in three aggressive prostate cancer cell lines [1].
• In a yeast two-hybrid screen a high-affinity interaction of myopodin with zyxin, a molecule known to regulate cell motility and migration, was identified [6].
• This sequence was mapped to chromosome 4q25 by screening the Genebridge 4 hamster radiation panel with primers specific to this probe, and subsequently identify a 54-kb minimal common deletion region that contains the sequence encoding myopodin [7].
• Differential nuclear expression for myopodin was identified among bladder cancer cell lines during cell-cycle [8].

Anatomical context of SYNPO2

• Sequence analysis indicates that myopodin shares significant homology with synaptopodin, a protein closely associated with podocyte and neuron differentiation [7].
• Normal urothelium expresses myopodin in the cytoplasm and nuclei [8].
• Mutation of 58KKRRRRARK66 into alanine residues blocks myopodin nuclear import and promotes formation of cytoplasmic actin filaments [9].
• Northern blots and immunofluorescence stainings show that the expression of myopodin is strongest in cross-striated muscle cells and smooth muscle cells [10]

Associations of SYNPO2 with chemical compounds

• METHODS: Immunostaining using anti-myopodin antibodies was performed on 746 formalin-fixed paraffin-embedded tissue samples to evaluate the level of myopodin expression in normal and malignant prostatic tissue [11].

Other interactions of SYNPO2

• Based on these findings, a nuclear export signal was identified in myopodin, a muscle-specific actin-binding protein, and the Bloom syndrome protein, a RecQ-like helicase [12].
• Myopodin-mediated suppression of prostate cancer cell migration involves interaction with zyxin [6].
• Myopodin, a synaptopodin homologue, is frequently deleted in invasive prostate cancers [7].

Analytical, diagnostic and therapeutic context of SYNPO2

• Myopodin colocalizes with alpha-actinin and is found at the Z-disc as shown by immunogold electron microscopy [2].
• The myopodin expression levels were examined in relation to prostate cancer grade and stage, preoperative prostate-specific antigen level, surgical margin involvement, tumor volume, and clinical relapse [11].
• OBJECTIVES: Myopodin has recently been characterized as a tumor suppressor gene whose encoded product inhibits prostate cancer growth and metastasis both in vitro and in animal models [11].

References