LPS-Stimulating Astrocyte-Conditioned Medium Causes Neuronal Apoptosis Via Increasing CDK11p58 Expression in PC12 Cells Through Downregulating AKT Pathway

Liu, Xiaojuan; Cheng, Chun; Shao, Bai; Wu, Xiaohong; Ji, Yuhong; Lü, Xiang; Shen, Aiguo

doi:10.1007/s10571-013-9945-4

Cited by 10 publications

(8 citation statements)

References 34 publications

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“…The functions of CDK11 have been proved to be linked with the regulation of cell cycle, RNA transcription and processing, neuronal function, and apoptosis 21 34 35 36 37 . The potential for CDK11 to regulate these diverse cellular activities is unique in the CDK family and highlights that CDK11 may exert critical regulatory roles in human tumorigenesis, cancer cell growth and proliferation.…”

Section: Discussionmentioning

confidence: 99%

Cyclin-dependent kinase 11p110 (CDK11p110) is crucial for human breast cancer cell proliferation and growth

Zhou

Han

et al. 2015

Sci Rep

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Cyclin-dependent kinases (CDKs) play important roles in the development of many types of cancers by binding with their paired cyclins. However, the function of CDK11 larger protein isomer, CDK11p110, in the tumorigenesis of human breast cancer remains unclear. In the present study, we explored the effects and molecular mechanisms of CDK11p110 in the proliferation and growth of breast cancer cells by determining the expression of CDK11p110 in breast tumor tissues and examining the phenotypic changes of breast cancer cells after CDK11p110 knockdown. We found that CDK11p110 was highly expressed in breast tumor tissues and cell lines. Tissue microarray analysis showed that elevated CDK11p110 expression in breast cancer tissues significantly correlated with poor differentiation, and was also associated with advanced TNM stage and poor clinical prognosis for breast cancer patients. In vitro knockdown of CDK11p110 by siRNA significantly inhibited cell growth and migration, and dramatically induced apoptosis in breast cancer cells. Flow cytometry demonstrated that cells were markedly arrested in G1 phase of the cell cycle after CDK11p110 downregulation. These findings suggest that CDK11p110 is critical for the proliferation and growth of breast cancer cells, which highlights CDK11p110 may be a promising therapeutic target for the treatment of breast cancer.

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Section: Discussionmentioning

confidence: 99%

Cyclin-dependent kinase 11p110 (CDK11p110) is crucial for human breast cancer cell proliferation and growth

Zhou

Han

et al. 2015

Sci Rep

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“…Among other members of the CDK family, CDK11 is involved in both cell cycle control and RNA transcription regulation. CDK11 is functionally relevant to many biologic processes, such as RNA transcription and splicing, mitosis, autophagy, and apoptosis [38, 45, 47, 56, 57]. Recently, distinct and unique biologic roles of CDK11 have been discovered in human cancers and in other human diseases [58].…”

Section: The Biology and Deregulation Of Cdks In Human Cancersmentioning

confidence: 99%

“…The functions of CDK11 have been proved to be linked with RNA transcription and processing, regulation of cell cycle, neuronal function, and apoptosis [38, 40, 47, 56, 58]. The potential for CDK11 to regulate these diverse cellular activities is unique in the CDK family and highlights that CDK11 may exert critical regulatory roles in human tumorigenesis and malignant characteristics of cancer cells.…”

Section: Distinct Specificity Of Cdk11mentioning

confidence: 99%

The emerging roles and therapeutic potential of cyclin-dependent kinase 11 (CDK11) in human cancer

et al. 2016

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Overexpression and/or hyperactivation of cyclin-dependent kinases (CDKs) are common features of most cancer types. CDKs have been shown to play important roles in tumor cell proliferation and growth by controlling cell cycle, transcription, and RNA splicing. CDK4/6 inhibitor palbociclib has been recently approved by the FDA for the treatment of breast cancer. CDK11 is a serine/threonine protein kinase in the CDK family and recent studies have shown that CDK11 also plays critical roles in cancer cell growth and proliferation. A variety of genetic and epigenetic events may cause universal overexpression of CDK11 in human cancers. Inhibition of CDK11 has been shown to lead to cancer cell death and apoptosis. Significant evidence has suggested that CDK11 may be a novel and promising therapeutic target for the treatment of cancers. This review will focus on the emerging roles of CDK11 in human cancers, and provide a proof-of-principle for continued efforts toward targeting CDK11 for effective cancer treatment.

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“…However, its expression in neuronal cells has previously been confirmed and a change in CDK11 cellular distribution has been associated with Alzheimer's disease (Bajic et al 2011). In addition, CDK11 p58 was found to modulate apoptosis in PC12 cells (a rat neuronal cell line) with this isoform promoting apoptosis (Liu et al 2013).…”

Section: Discussionmentioning

confidence: 97%

Differential expression of cyclin-dependent kinases in the adult human retina in relation to CDK inhibitor retinotoxicity

et al. 2019

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Cyclin-dependent kinases (CDKs) are a family of kinases associated predominantly with cell cycle control, making CDK inhibitors interesting candidates for anti-cancer therapeutics. However, retinal toxicity (loss of photoreceptors) has been associated with CDK inhibitors, including the pan-CDK inhibitor AG-012896. The purpose of this research was to use a novel planar sectioning technique to determine CDK expression profiles in the ex vivo human retina with the aim of identifying isoforms responsible for CDK retinotoxicity. Four CDK isoforms (CDK11, 16, 17 and 18) were selected as a result of IC 50 data comparing neurotoxic (AG-012986 and NVP-1) and non-neurotoxic (dinaciclib and NVP-2) CDK inhibitors, with IC 50 s at CDK11 showing a clear difference between the neurotoxic and non-neurotoxic drugs. CDK11 was maximally expressed in the photoreceptor layer, whereas CDK16, 17 and 18 showed maximal expression in the inner nuclear layer. CDK5 (an isoform associated with retinal homeostasis) was maximally expressed in the retinal ganglion cell layer. Apart from CDK18, each isoform showed expression in the photoreceptor layer. The human Müller cell line MIO-M1 expressed CDK5, 11, 16 and 17 and AG-01298 (0.02-60 µM) caused a dose-dependent increase in MIO-M1 cell death. In conclusion, CDK11 appears the most likely candidate for mediation of photoreceptor toxicity. RNA profiling can be used to determine the distribution of genes of interest in relation to retinal toxicity in the human retina.

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LPS-Stimulating Astrocyte-Conditioned Medium Causes Neuronal Apoptosis Via Increasing CDK11p58 Expression in PC12 Cells Through Downregulating AKT Pathway

Cited by 10 publications

References 34 publications

Cyclin-dependent kinase 11p110 (CDK11p110) is crucial for human breast cancer cell proliferation and growth

Cyclin-dependent kinase 11p110 (CDK11p110) is crucial for human breast cancer cell proliferation and growth

The emerging roles and therapeutic potential of cyclin-dependent kinase 11 (CDK11) in human cancer

Differential expression of cyclin-dependent kinases in the adult human retina in relation to CDK inhibitor retinotoxicity

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