Abi enhances Abl-mediated Cdc2 phosphorylation and inactivation

Lin, Tzu-Yang; Huang, Chiu-Hui; Chou, Wen-Gang; Juang, Jyh‐Lyh

doi:10.1007/bf02254375

Cited by 29 publications

(18 citation statements)

References 25 publications

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“…Supporting this model, one very recent study has 3105 RESEARCH ARTICLE Abi suppresses Abl in Drosophila demonstrated that Abl can inhibit the role of Abi in the engulfment of apoptotic cells in C. elegans (Hurwitz et al, 2009). Given that Abi is the Abl kinase substrate and that it also functions as an adaptor protein for Abl in regulating other downstream effectors (Juang and Hoffmann, 1999;Tani et al, 2003;Lin et al, 2004;Leng et al, 2005;Maruoka et al, 2005) Since our data suggest an antagonistic interaction between abi and Abl for the CNS and NMJ phenotypes (Fig. 2), we speculated that Abl heterozygosity would suppress the semilethal phenotype of abi mutants.…”

Section: Discussionmentioning

confidence: 95%

“…Abi was first identified as an Abl kinase substrate, functioning in modulating the transformation activity of oncogenic Abl in human cancers (Dai and Pendergast, 1995;Shi et al, 1995;Wang et al, 2007;Yu et al, 2008). Intriguingly, we and others have shown that Abi also functions as an activator of Abl kinase activity (Juang and Hoffmann, 1999;Tani et al, 2003;Lin et al, 2004;Leng et al, 2005;Maruoka et al, 2005). Moreover, the interaction of Abl and Abi can trigger an array of biochemical and functional changes in Abi, including protein phosphorylation, stability and subcellular localization (Huang et al, 2007), which might ultimately lead to the control of a particular biological process in vivo.…”

Section: Discussionmentioning

confidence: 98%

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Abi plays an opposing role to Abl inDrosophilaaxonogenesis and synaptogenesis

et al. 2009

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Abl tyrosine kinase (Abl) regulates axon guidance by modulating actin dynamics. Abelson interacting protein (Abi), originally identified as a kinase substrate of Abl, also plays a key role in actin dynamics, yet its role with respect to Abl in the developing nervous system remains unclear. Here we show that mutations in abi disrupt axonal patterning in the developing Drosophila central nervous system (CNS). However, reducing abi gene dosage by half substantially rescues Abl mutant phenotypes in pupal lethality, axonal guidance defects and locomotion deficits. Moreover, we show that mutations in Abl increase synaptic growth and spontaneous synaptic transmission frequency at the neuromuscular junction. Double heterozygosity for abi and enabled(ena) also suppresses the synaptic overgrowth phenotypes of Abl mutants, suggesting that Abi acts cooperatively with Ena to antagonize Abl function in synaptogenesis. Intriguingly, overexpressing Abi or Ena alone in cultured cells dramatically redistributed peripheral F-actin to the cytoplasm, with aggregates colocalizing with Abi and/or Ena, and resulted in a reduction in neurite extension. However, co-expressing Abl with Abi or Ena redistributed cytoplasmic F-actin back to the cell periphery and restored bipolar cell morphology. These data suggest that abi and Ablhave an antagonistic interaction in Drosophila axonogenesis and synaptogenesis, which possibly occurs through the modulation of F-actin reorganization.

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Section: Discussionmentioning

confidence: 95%

Section: Discussionmentioning

confidence: 98%

Abi plays an opposing role to Abl inDrosophilaaxonogenesis and synaptogenesis

et al. 2009

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“…In the present study, we identified Abi2 as a protein that binds to TRIM32, suggesting a novel mechanism of TRIM32 in carcinogenesis in human head and neck squamous cell carcinoma. We focused on Abi2 among candidates detected by yeast-two hybrid screening because it has been reported that Abi2 suppresses cell growth (23) and that a truncated form accelerates the tumorigenesis (22). Theses previous reports suggest that Abi2 functions as a tumor suppressor.…”

Section: Discussionmentioning

confidence: 99%

“…Abi2 promotes Abl-mediated phosphorylation of Cdc2 and inactivation of Cdc2 kinase activity, leading to suppression of cell growth (23). Coexpression of a truncated form of Abi2 with c-Abl activates the oncogenic potential of c-Abl, suggesting that the full-length Abi2 functions as a tumor suppressor (22).…”

Section: Introductionmentioning

confidence: 99%

Tripartite Motif Protein 32 Facilitates Cell Growth and Migration via Degradation of Abl-Interactor 2

et al. 2008

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Tripartite motif protein 32 (TRIM32) mRNA has been reported to be highly expressed in human head and neck squamous cell carcinoma, but the involvement of TRIM32 in carcinogenesis has not been fully elucidated. In this study, we found by using yeast two-hybrid screening that TRIM32 binds to Ablinteractor 2 (Abi2), which is known as a tumor suppressor and a cell migration inhibitor, and we showed that TRIM32 mediates the ubiquitination of Abi2. Overexpression of TRIM32 promoted degradation of Abi2, resulting in enhancement of cell growth, transforming activity, and cell motility, whereas a dominant-negative mutant of TRIM32 lacking the RING domain inhibited the degradation of Abi2. In addition, we found that TRIM32 suppresses apoptosis induced by cisdiamminedichloroplatinum (II) in HEp2 cell lines. These findings suggest that TRIM32 is a novel oncogene that promotes tumor growth, metastasis, and resistance to anticancer drugs. [Cancer Res 2008;68(14):5572-80]

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“…Cell lysate was produced in lysis buffer or extract buffer 38 for Cdk5 immunoprecipitation. Proteins were analyzed by direct Western blotting (30 mg/lane) or blotting after immunoprecipitation (1-2 mg/immunoprecipitation).…”

Section: Methodsmentioning

confidence: 99%

Abl deregulates Cdk5 kinase activity and subcellular localization in Drosophila neurodegeneration

Lin

2006

Cell Death Differ

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Although Abl functions in mature neurons, work to date has not addressed Abl's role on Cdk5 in neurodegeneration. We found that b-amyloid (Ab42) initiated Abl kinase activity and that blockade of Abl kinase rescued both Drosophila and mammalian neuronal cells from cell death. We also found activated Abl kinase to be necessary for the binding, activation, and translocalization of Cdk5 in Drosophila neuronal cells. Conversion of p35 into p25 was not observed in Ab42-triggered Drosophila neurodegeneration, suggesting that Cdk5 activation and protein translocalization can be p25-independent. Our genetic studies also showed that abl mutations repressed Ab42-induced Cdk5 activity and neurodegeneration in Drosophila eyes. Although Ab42 induced conversion of p35 to p25 in mammalian cells, it did not sufficiently induce Cdk5 activation when c-Abl kinase activity was suppressed. Therefore, we propose that Abl and p35/p25 cooperate in promoting Cdk5-pY15, which deregulates Cdk5 activity and subcellular localization in Ab42-triggered neurodegeneration. Alzheimer's disease (AD), the most frequently diagnosed neurodegenerative disease, is characterized histologically by two hallmark features: senile plaques, which are extracellular deposits of b-amyloid(Ab42), and intracellular neurofibrillary tangles of aggregated hyperphosphorylated tau protein.1 The accumulation of Ab42 has been found to precede the pathological neurodegenerational changes, 2 and the inhibition of Ab42 accumulation by amyloid vaccination can effectively prevent the pathogenesis in mammalian AD animals.3 Less clear is the downstream protein targets of Ab42 toxicity in neurons. Thus, study of the Ab42-induced signaling cascade is of interest because it may provide clues for designing therapeutic strategies for the treatment of AD. AD brain samples show elevated cdk5 activity, 4 and deregulated Cdk5 has been associated with the tau hyperphosphorylation, a state leading to AD.5 Like other Cdk members, Cdk5 needs to bind with its regulatory partners to activate kinase activity. One of Cdk5's activating partners, p35, is expressed primarily in postmitotic neurons.6 Cdk5 also appears to be deregulated by its association with p25, a calpain digestion product of p35 in AD neurons. 7 The Cdk5/ p25 complex is thought to hyperphosphorylate tau and reduce tau's association with microtubules, resulting in neuronal apoptosis.8 Recently, c-Abl has been reported to phosphorylate and activate Cdk5 through the adaptor protein Cables during brain development. 9 The integration of Abl and Cdk5 into the same biological pathway suggests they have similar roles in neuronal cytoskeletal regulation and axon guidance.The Abl kinase, apparently evolutionarily conserved from flies to humans, is involved in the development of the nervous system. 10 Based on genetic studies of mice 11 and Drosophila, 12 abl mutations may lead to neuronal defects. Abl kinase has also been implicated in the regulation of apoptosis. 13Interestingly, the cytotoxicity of Ab42 is considered a crucial stress f...

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Abi enhances Abl-mediated Cdc2 phosphorylation and inactivation

Cited by 29 publications

References 25 publications

Abi plays an opposing role to Abl inDrosophilaaxonogenesis and synaptogenesis

Abi plays an opposing role to Abl inDrosophilaaxonogenesis and synaptogenesis

Tripartite Motif Protein 32 Facilitates Cell Growth and Migration via Degradation of Abl-Interactor 2

Abl deregulates Cdk5 kinase activity and subcellular localization in Drosophila neurodegeneration

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