Expression of AIE-75 PDZ-domain protein induces G2/M cell cycle arrest in human colorectal adenocarcinoma SW480 cells

Hirai, Atsuko; Tada, Mitsuhiro; Furuuchi, Keiji; Ishikawa, Susumu; Makiyama, Kokonoe; Hamada, Junichi; Okada, Futoshi; Kobayashi, Ichiro; Fukuda, Hiroshi; Moriuchi, Tetsuya

doi:10.1016/j.canlet.2004.02.005

Cited by 9 publications

(6 citation statements)

References 28 publications

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“…We also observed strong expression of ush1c in the gut and swim bladder, and weaker expression in the brain and trunk muscles (Fig. 1B), consistent with reported expression in human tissues (Verpy et al, 2000; Hirai et al, 2004). …”

Section: Resultssupporting

confidence: 90%

Harmonin (Ush1c) is required in zebrafish Müller glial cells for photoreceptor synaptic development and function

Phillips

Blanco-Sánchez

Lentz

et al. 2011

Disease Models &Amp; Mechanisms

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SUMMARYUsher syndrome is the most prevalent cause of hereditary deaf-blindness, characterized by congenital sensorineural hearing impairment and progressive photoreceptor degeneration beginning in childhood or adolescence. Diagnosis and management of this disease are complex, and the molecular changes underlying sensory cell impairment remain poorly understood. Here we characterize two zebrafish models for a severe form of Usher syndrome, Usher syndrome type 1C (USH1C): one model is a mutant with a newly identified ush1c nonsense mutation, and the other is a morpholino knockdown of ush1c. Both have defects in hearing, balance and visual function from the first week of life. Histological analyses reveal specific defects in sensory cell structure that are consistent with these behavioral phenotypes and could implicate Müller glia in the retinal pathology of Usher syndrome. This study shows that visual defects associated with loss of ush1c function in zebrafish can be detected from the onset of vision, and thus could be applicable to early diagnosis for USH1C patients.

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Section: Resultssupporting

confidence: 90%

Harmonin (Ush1c) is required in zebrafish Müller glial cells for photoreceptor synaptic development and function

Phillips

Blanco-Sánchez

Lentz

et al. 2011

Disease Models &Amp; Mechanisms

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“…Because PTPN13 can dephosphorylate tyrosine residues of the clustered ephrin B1, we predicted that the formation of ephrin B1, NHERF1, and other PDZ domain-containing protein phosphatases (PP) such as PTPN13 and PP2C can produce a scaffold membrane-associated protein cluster and that the protein complex can dephosphorylate ephrin B1 and TAZ (25,40). To test the prediction, we performed coimmunoprecipitation again with the antibody specific to NHERF1 to pull down the NHERF1 protein complex.…”

Section: Resultsmentioning

confidence: 99%

Ephrin B1 Regulates Bone Marrow Stromal Cell Differentiation and Bone Formation by Influencing TAZ Transactivation via Complex Formation with NHERF1

Xing

Kim

Wergedal

et al. 2010

Molecular and Cellular Biology

119

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Mutations of ephrin B1 in humans result in craniofrontonasal syndrome. Because little is known of the role and mechanism of action of ephrin B1 in bone, we examined the function of osteoblast-produced ephrin B1 in vivo and identified the molecular mechanism by which ephrin B1 reverse signaling regulates bone formation. Targeted deletion of the ephrin B1 gene in type 1␣2 collagen-producing cells resulted in severe calvarial defects, decreased bone size, bone mineral density, and trabecular bone volume, caused by impairment in osterix expression and osteoblast differentiation. Coimmunoprecipitation of the TAZ complex with TAZspecific antibody revealed a protein complex containing ephrin B1, PTPN13, NHERF1, and TAZ in bone marrow stromal (BMS) cells. Activation of ephrin B1 reverse signaling with soluble EphB2-Fc led to a time-dependent increase in TAZ dephosphorylation and shuttling from cytoplasm to nucleus. Treatment of BMS cells with exogenous EphB2-Fc resulted in a 4-fold increase in osterix expression as determined by Western blotting. Disruption of TAZ expression using specific lentivirus small hairpin RNA (shRNA) decreased TAZ mRNA by 80% and ephrin B1 reverse signaling-mediated increases in osterix mRNA by 75%. Knockdown of NHERF1 expression reduced basal levels of osterix expression by 90% and abolished ephrin B1-mediated induction of osterix expression. We conclude that locally produced ephrin B1 mediates its effects on osteoblast differentiation by a novel molecular mechanism in which activation of reverse signaling leads to dephosphorylation of TAZ and subsequent release of TAZ from the ephrin B1/NHERF1/TAZ complex to translocate to the nucleus to induce expression of the osterix gene and perhaps other osteoblast differentiation genes. Our findings provide strong evidence that ephrin B1 reverse signaling in osteoblasts is critical for BMS cell differentiation and bone formation.Osteoporosis is a common disease characterized by an agedependent decrease in bone mineral density (BMD) and a microarchitectural deterioration of bone tissue, with a consequent increase in the risk of developing fragility fractures of the hip, spine, and other skeletal sites (19). The decrease in bone mass occurs when the body fails to form enough new bone to replace the amount of old bone resorbed leading to reduced bone strength. There are two major known causes of osteoporosis: low peak BMD, which is typically achieved by around age 30, and high bone loss rate, which occurs particularly after menopause and during the natural process of aging. The accumulation of peak bone mass depends on bone growth during early skeletal development and the balance between osteoblastic bone formation and osteoclastic bone resorption during the postnatal growth period. Therefore, understanding the regulatory factors that govern bone development, bone size, bone mineralization, and bone quality during active growth periods as well as bone homeostasis during menopause and aging is essential for development of therapeutics to prevent osteoporosi...

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“…Examples include stroke (Sattler et al, 1999; Aarts et al, 2002), cancers (Kanamori et al, 2003;Hirai et al, 2004;Doorbar, 2006), infection (Excoffon et al, 2004;Xie et al, 2006), and disorders of lipid metabolism (Yesilaltay et al, 2005). Although we focused on relevant PDZ interactions of NMDAR subunits and of Tat-NR2B9c, the broader utility of this interaction assay as a drug discovery platform is evident.…”

Section: Pdz Domain Interaction Assaymentioning

confidence: 99%

PDZ Protein Interactions Underlying NMDA Receptor-Mediated Excitotoxicity and Neuroprotection by PSD-95 Inhibitors

Cui¹,

Hayashi²,

Sun³

et al. 2007

J. Neurosci.

187

149

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In neuronal synapses, PDZ domains [postsynaptic density-95 (PSD-95)/Discs large/zona occludens-1] of PSD-95 proteins interact with C termini of NMDA receptor [NMDAR (NR)]subunits, linking them to downstream neurotoxic signaling molecules. Perturbing NMDAR/ PSD-95 interactions with a Tat peptide comprising the nine C-terminal residues of the NR2B subunit (Tat-NR2B9c) reduces neurons' vulnerability to excitotoxicity and ischemia. However, NR subunit C termini may bind many of Ͼ240 cellular PDZs, any of which could mediate neurotoxic signaling independently of PSD-95. Here, we performed a proteomic and biochemical analysis of the interactions of all known human PDZs with synaptic signaling proteins including NR1, NR2A-NR2D, and neuronal nitric oxide synthase (nNOS). Tat-NR2B9c, whose interactions define PDZs involved in neurotoxic signaling, was also used. NR2A-NR2D subunits and Tat-NR2B9c had similar, highly specific, PDZ protein interactions, of which the strongest were with the PSD-95 family members (PSD-95, PSD-93, SAP97, and SAP102) and Tax interaction protein 1 (TIP1). The PSD-95 PDZ2 domain bound NR2A-NR2C subunits most strongly (EC 50 , ϳ1 M), and fusing the NR2B C terminus to Tat enhanced its affinity for PSD-95 PDZ2 by Ͼ100-fold (EC 50 , ϳ7 nM). IC 50 values for Tat-NR2B9c inhibiting NR2A-NR2C/PSD-95 interactions (ϳ1-10 M) and nNOS/PSD-95 interactions (200 nM) confirmed the feasibility of such inhibition. To determine which of the PDZ interactions of Tat-NR2B9c mediate neuroprotection, one of PSD-95, PSD-93, SAP97, SAP102, TIP1, or nNOS expression was inhibited in cortical neurons exposed to NMDA toxicity. Only neurons lacking PSD-95 or nNOS but not PSD-93, SAP97, SAP102, or TIP1 exhibited reduced excitotoxic vulnerability. Thus, despite the ubiquitousness of PDZ domaincontaining proteins, PSD-95 and nNOS above any other PDZ proteins are keys in effecting NMDAR-dependent excitotoxicity. Consequently, PSD-95 inhibition may constitute a highly specific strategy for treating excitotoxic disorders.

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Expression of AIE-75 PDZ-domain protein induces G2/M cell cycle arrest in human colorectal adenocarcinoma SW480 cells

Cited by 9 publications

References 28 publications

Harmonin (Ush1c) is required in zebrafish Müller glial cells for photoreceptor synaptic development and function

Harmonin (Ush1c) is required in zebrafish Müller glial cells for photoreceptor synaptic development and function

Ephrin B1 Regulates Bone Marrow Stromal Cell Differentiation and Bone Formation by Influencing TAZ Transactivation via Complex Formation with NHERF1

PDZ Protein Interactions Underlying NMDA Receptor-Mediated Excitotoxicity and Neuroprotection by PSD-95 Inhibitors

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