Characterization of an alternatively spliced AATYK mRNA: Expression pattern of AATYK in the brain and neuronal cells

Baker, Stacey J.; Sumerson, Rachel; Reddy, C. Devendranath; Berrebi, Albert S.; Flynn, Daniel C.; Reddy, E. Premkumar

doi:10.1038/sj.onc.1204209

Cited by 42 publications

(42 citation statements)

References 15 publications

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“…Cloning and characterization of the cDNA encoding CD30 established the protein as a member of the tumor necrosis factor receptor (TNFR) superfamily (DuÈ rkop et al, 1992). This family of cytokine receptors is de®ned by sequence homology in the cysteine rich repeats of the extracellular domains (Smith et al, 1994;Baker and Reddy, 1996). The intracellular parts of the cytokine receptors share no homologue elements, except the so-called death domain, a sequence motif for protein-interaction with death-inducing signal molecules (Ware et al, 1996, Askenazi et al, 1999Baker and Reddy, 1998).…”

Section: Introductionmentioning

confidence: 99%

CD30-mediated cell cycle arrest associated with induced expression of p21CIP1/WAF1 in the anaplastic large cell lymphoma cell line Karpas 299

et al. 2001

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One of the major characteristics of anaplastic large cell lymphomas (ALCL) is the expression of the Ki-1/CD30 antigen. While the receptor mediates NF-kB-activation in Hodgkin's lymphomas, some data suggest the CD30-mediated apoptosis of other CD30-expressing cells. We were able to demonstrate that activation of CD30 leads to dierent eects regarding cell proliferation of the ALCL-derived cell lines Karpas 299 and JB6. Western and Northern blotting analysis revealed that CD30-induced growth inhibition of Karpas 299 cells correlated with a strong upregulation of the cell cycle inhibitor p21. We found a non activating point mutation at codon 273 in exon 8 of the p53 gene in Karpas 299 cells which indicates an p53-independent mechanism for induced p21 expression. Abundant p21 protein expression resulted in hypophosphorylation of the retinoblastoma protein (Rb) and inhibition of the proliferating cell nuclear antigen (PCNA). CD30-stimulated cells showed no indications of apoptotic cell death, like genomic DNA fragmentation or cleavage of the caspase-3 target protein poly (ADP-ribose) polymerase (PARP). Our results indicate that CD30 is able to mediate an p21-associated cell cycle arrest in ALCL with possible implications for prognosis and clinical treatment. Oncogene (2001) 20, 590 ± 598.

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Section: Introductionmentioning

confidence: 99%

CD30-mediated cell cycle arrest associated with induced expression of p21CIP1/WAF1 in the anaplastic large cell lymphoma cell line Karpas 299

et al. 2001

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“…These clinical observations suggest that ethanol exposure enhances hepatic vulnerability to a secondary inflammatory or oxidative stress, such that serious liver injury is most likely to occur when proinflammatory/pro-oxidant factors are superimposed onto a background of ethanol use (10). Because tumor necrosis factor-␣ ((TNF␣) 1 and cytokines that potentiate TNF activity are the common, proximal mediators of inflammatory liver injury (11)(12)(13), several laboratories have been evaluating the possibility that ethanol may sensitize hepatocytes to TNFrelated toxicity (14 -18). The evidence supporting this concept is growing.…”

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Chronic Ethanol Exposure Potentiates Lipopolysaccharide Liver Injury Despite Inhibiting Jun N-terminal Kinase and Caspase 3 Activation

Koteish

Yang

Lin

et al. 2002

Journal of Biological Chemistry

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Although ethanol is known to sensitize hepatocytes to tumor necrosis factor (TNF) lethality, the mechanisms involved remain controversial. Recently, others have shown that adding TNF␣ to cultures of ethanol-pretreated hepatocytes provokes the mitochondrial permeability transition, cytochrome c release, procaspase 3 activation, and apoptosis. Although this demonstrates that ethanol can sensitize hepatocytes to TNF-mediated apoptosis, the hepatic inflammation and ballooning hepatocyte degeneration that typify alcohol-induced liver injury suggest that other mechanisms might predominate in vivo. To evaluate this possibility, acute responses to lipopolysaccharide (LPS), a potent inducer of TNF␣, were compared in mice that had been fed either an ethanol-containing or control diet for 5 weeks. Despite enhanced induction of cytokines such as interleukin (IL)-10, IL-15, and IL-6 that protect hepatocytes from apoptosis, ethanol-fed mice exhibited a 4 -5-fold increase in serum alanine aminotransferase after LPS, confirming increased liver injury. Six h post-LPS histology also differed notably in the two groups, with control livers demonstrating only scattered apoptotic hepatocytes, whereas ethanol-exposed livers had large foci of ballooned hepatocytes, inflammation, and scattered hemorrhage. No caspase 3 activity was noted during the initial 6 h after LPS in ethanol-fed mice, but this tripled by 1.5 h after LPS in controls. Procaspase 8 cleavage and activity of the apoptosis-associated kinase, Jun N-terminal kinase, were also greater in controls. In contrast, ethanol exposure did not inhibit activation of cytoprotective mitogen-activated protein kinases and AKT or attenuate induction of the anti-apoptotic factors NF-B and inducible nitric oxide synthase. Consistent with these responses, neither cytochrome c release, an early apoptotic response, nor hepatic oligonucleosomal DNA fragmentation, the ultimate consequence of apoptosis, was increased by ethanol. Thus, ethanol exacerbates TNF-related hepatotoxicity in vivo without enhancing caspase 3-dependent apoptosis.

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“…AATKA encodes a cytoplasmic protein with an open reading frame of 1317 amino acids, whereas AATKB contains an additional transmembrane domain at the N-terminus, which adds 57 amino acids. 4,5 Functional differences between the two isoforms have never been addressed. Most functional studies of AATK have been focused on the nervous system.…”

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Apoptosis-associated tyrosine kinase 1 inhibits growth and migration and promotes apoptosis in melanoma

Rubin

2014

Laboratory Investigation

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Apoptosis-associated tyrosine kinase 1 (AATK1) was initially identified as a protein that was dramatically overexpressed during growth arrest and apoptosis of 32Dcl myeloblastic leukemia cells. AATK is expressed in different regions of the brain and may have a role in normal nervous system development by its dual functions of enhancing apoptosis of mature granule cells and promoting terminal neuronal differentiation of developing neurons. However, its function in cancer has never been studied. Melanoma is a tumor composed of transformed cells within the melanocyte lineage deriving from the embryonic neural crest. It has been shown that developmental pathways in neural crest cells have a direct bearing on melanoma formation and human metastatic melanoma cells express a dedifferentiated phenotype. We found that the expression levels of AATK are lower in metastatic melanoma cell lines compared with primary melanoma cell lines and normal human melanocytes. We found that depletion of AATK mRNA in metastatic melanoma cell lines enhanced cell migration in cell line derived from metastatic melanomas. Overexpression of AATK inhibited cell proliferation, colony formation, and promoted apoptosis in melanoma cell lines derived from primary and metastatic melanomas. Signal transduction pathway analysis revealed that Src is involved in regulating AATK. Our results demonstrate for the first time that AATK inhibits cell proliferation, colony formation, and migration, and also promotes apoptosis in melanoma cells.

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Characterization of an alternatively spliced AATYK mRNA: Expression pattern of AATYK in the brain and neuronal cells

Cited by 42 publications

References 15 publications

CD30-mediated cell cycle arrest associated with induced expression of p21CIP1/WAF1 in the anaplastic large cell lymphoma cell line Karpas 299

CD30-mediated cell cycle arrest associated with induced expression of p21CIP1/WAF1 in the anaplastic large cell lymphoma cell line Karpas 299

Chronic Ethanol Exposure Potentiates Lipopolysaccharide Liver Injury Despite Inhibiting Jun N-terminal Kinase and Caspase 3 Activation

Apoptosis-associated tyrosine kinase 1 inhibits growth and migration and promotes apoptosis in melanoma

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