Nemo‐like kinase promotes etoposide‐induced apoptosis of male germ cell‐derived GC‐1 cells in vitro

Cheng, Xiaowen; Liang, Junbo; Teng, Yuee; Fu, Jun; Miao, Shiying; Zong, Shudong; Wang, Linfang

doi:10.1016/j.febslet.2012.04.005

Cited by 7 publications

(6 citation statements)

References 38 publications

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“…More importantly, deletion of Nlk specifically from the heart, either during embryonic development or for the first time in adults, reduced the hypertrophic response to pressure overload stimulation and lessened propensity towards heart failure and reduced cardiac functional capacity. Finally, heart-specific deletion of Nlk significantly protected the heart from I/R injury, consistent with its previous description as a regulator of apoptosis in cultured cells [ 9 , 23 ]. Taken together, these observations indicate that NLK is a maladaptive signaling kinase in the heart that mediates disease, hence it represents a novel target for potential pharmacologic intervention in treating human heart disease, and as such, selective kinase inhibitors should be developed.…”

Section: Discussionsupporting

confidence: 90%

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Nemo-Like Kinase (NLK) Is a Pathological Signaling Effector in the Mouse Heart

et al. 2016

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Nemo-like kinase (NLK) is an evolutionary conserved serine/threonine protein kinase implicated in development, proliferation and apoptosis regulation. Here we identified NLK as a gene product induced in the hearts of mice subjected to pressure overload or myocardial infarction injury, suggesting a potential regulatory role with pathological stimulation to this organ. To examine the potential functional consequences of increased NLK levels, cardiac-specific transgenic mice with inducible expression of this gene product were generated, as well as cardiac-specific Nlk gene-deleted mice. NLK transgenic mice demonstrated baseline cardiac hypertrophy, dilation, interstitial fibrosis, apoptosis and progression towards heart failure in response to two surgery-induced cardiac disease models. In contrast, cardiac-specific deletion of Nlk from the heart, achieved by crossing a Nlk-loxP allele containing mouse with either a mouse containing a β-myosin heavy chain promoter driven Cre transgene or a tamoxifen inducible α-myosin heavy chain promoter containing transgene driving a MerCreMer cDNA, protected the mice from cardiac dysfunction following pathological stimuli. Mechanistically, NLK interacted with multiple proteins including the transcription factor Stat1, which was significantly increased in the hearts of NLK transgenic mice. These results indicate that NLK is a pathological effector in the heart.

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Section: Discussionsupporting

confidence: 90%

“…In other genetic backgrounds Nlk -/- mice are either embryonic lethal or they survive 4–6 weeks but then die from hematopoietic cell abnormalities with defective bone marrow stroma [ 7 ]. NLK also induces apoptotic cell death in multiple mammalian cell types [ 8 , 9 ].…”

Section: Introductionmentioning

confidence: 99%

Nemo-Like Kinase (NLK) Is a Pathological Signaling Effector in the Mouse Heart

et al. 2016

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“…The production of retrovirus has been described previously [18]. Briefly, retroviral vectors expressing either Flag-StrepII-SKAP or Flag-StrepII-RFP were co-transfected with helper plasmids containing gag-pol and env into HEK-293T cells.…”

Section: Methodsmentioning

confidence: 99%

Small Kinetochore Associated Protein (SKAP) Promotes UV-Induced Cell Apoptosis through Negatively Regulating Pre-mRNA Processing Factor 19 (Prp19)

Wang

Cai

et al. 2014

PLoS ONE

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Apoptosis is a regulated cellular suicide program that is critical for the development and maintenance of healthy tissues. Previous studies have shown that small kinetochore associated protein (SKAP) cooperates with kinetochore and mitotic spindle proteins to regulate mitosis. However, the role of SKAP in apoptosis has not been investigated. We have identified a new interaction involving SKAP, and we propose a mechanism through which SKAP regulates cell apoptosis. Our experiments demonstrate that both overexpression and knockdown of SKAP sensitize cells to UV-induced apoptosis. Further study has revealed that SKAP interacts with Pre-mRNA processing Factor 19 (Prp19). We find that UV-induced apoptosis can be inhibited by ectopic expression of Prp19, whereas silencing Prp19 has the opposite effect. Additionally, SKAP negatively regulates the protein levels of Prp19, whereas Prp19 does not alter SKAP expression. Finally, rescue experiments demonstrate that the pro-apoptotic role of SKAP is executed through Prp19. Taken together, these findings suggest that SKAP promotes UV-induced cell apoptosis by negatively regulating the anti-apoptotic protein Prp19.

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“…NLK was initially shown to be involved in various developmental processes, such as the promotion of mesoderm specification in sea urchins [32], mesoderm patterning, patterning of midbrain and forebrain in zebrafish [33], as well as oocyte maturation in Xenopus Laevis [34] and in mouse testes [35].…”

Section: Nlk and Developmentmentioning

confidence: 99%

Nemo-Like Kinase in Development and Diseases: Insights from Mouse Studies

Daams

Massoumi

2020

IJMS

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The Wnt signalling pathway is a central communication cascade between cells to orchestrate polarity and fate during development and adult tissue homeostasis in various organisms. This pathway can be regulated by different signalling molecules in several steps. One of the coordinators in this pathway is Nemo-like kinase (NLK), which is an atypical proline-directed serine/threonine mitogen-activated protein (MAP) kinase. Very recently, NLK was established as an essential regulator in different cellular processes and abnormal NLK expression was highlighted to affect the development and progression of various diseases. In this review, we focused on the recent discoveries by using NLK-deficient mice, which show a phenotype in the development and function of organs such as the lung, heart and skeleton. Furthermore, NLK could conduct the function and differentiation of cells from the immune system, in addition to regulating neurodegenerative diseases, such as Huntington’s disease and spinocerebellar ataxias. Overall, generations of NLK-deficient mice have taught us valuable lessons about the role of this kinase in certain diseases and development.

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Nemo‐like kinase promotes etoposide‐induced apoptosis of male germ cell‐derived GC‐1 cells in vitro

Cited by 7 publications

References 38 publications

Nemo-Like Kinase (NLK) Is a Pathological Signaling Effector in the Mouse Heart

Nemo-Like Kinase (NLK) Is a Pathological Signaling Effector in the Mouse Heart

Small Kinetochore Associated Protein (SKAP) Promotes UV-Induced Cell Apoptosis through Negatively Regulating Pre-mRNA Processing Factor 19 (Prp19)

Nemo-Like Kinase in Development and Diseases: Insights from Mouse Studies

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