Nek family of kinases in cell cycle, checkpoint control and cancer

Moniz, Larissa S.; Dutt, Previn; Haider, Nasir; Stambolic, Vuk

doi:10.1186/1747-1028-6-18

Cited by 117 publications

(104 citation statements)

References 86 publications

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“…5A and B). Previous reports showed that NEK kinases, including NEK7, play important roles in the cell-cycle checkpoint regulation at G 1 -S, intra-S, and G 2 -M phases in addition to their established functions during mitosis (39,40), and our results appear to be consistent with these findings. In addition, we prepared cell lysates 24 hours after the release of cell cycle and conducted Western blotting for phosphorylated H3 Serine 10, a maker of mitosis.…”

Section: Direct Regulation Nek7 Transcription By Whsc1supporting

confidence: 93%

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WHSC1 Promotes Oncogenesis through Regulation of NIMA-Related Kinase-7 in Squamous Cell Carcinoma of the Head and Neck

Saloura

Cho

Kiyotani

et al. 2015

Molecular Cancer Research

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Squamous cell carcinoma of the head and neck (SCCHN) is a relatively common malignancy with suboptimal long-term prognosis, thus new treatment strategies are urgently needed. Over the last decade, histone methyltransferases (HMT) have been recognized as promising targets for cancer therapy, but their mechanism of action in most solid tumors, including SCCHN, remains to be elucidated. This study investigated the role of Wolf-Hirschhorn syndrome candidate 1 (WHSC1), an NSD family HMT, in SCCHN. Immunohistochemical analysis of locoregionally advanced SCCHN, dysplastic, and normal epithelial tissue specimens revealed that WHSC1 expression and dimethylation of histone H3 lysine 36 (H3K36me2) were significantly higher in SCCHN tissues than in normal epithelium. Both WHSC1 expression and H3K36me2 levels were significantly correlated with histologic grade. WHSC1 knockdown in multiple SCCHN cell lines resulted in significant growth suppression, induction of apoptosis, and delay of the cell-cycle progression. Immunoblot and immunocytochemical analyses in SCCHN cells demonstrated that WHSC1 induced H3K36me2 and H3K36me3. Microarray expression profile analysis revealed NIMA-related kinase-7 (NEK7) to be a downstream target gene of WHSC1, and chromatin immunoprecipitation (ChIP) assays showed that NEK7 was directly regulated by WHSC1 through H3K36me2. Furthermore, similar to WHSC1, NEK7 knockdown significantly reduced cell-cycle progression, indicating that NEK7 is a key player in the molecular pathway regulated by WHSC1.Implications: WHSC1 possesses oncogenic functions in SCCHN and represents a potential molecular target for the treatment of SCCHN. Mol Cancer Res; 13(2); 293-304. Ó2014 AACR.

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Section: Direct Regulation Nek7 Transcription By Whsc1supporting

confidence: 93%

“…S4). Among these genes, NEK7 was previously reported to regulate proliferation of cancer cells (36,39), which was a phenotype observed with WHSC1 knockdown. In addition, NEK7 was confirmed to be significantly decreased after knockdown of WHSC1 at the protein level.…”

Section: Direct Regulation Nek7 Transcription By Whsc1mentioning

confidence: 93%

WHSC1 Promotes Oncogenesis through Regulation of NIMA-Related Kinase-7 in Squamous Cell Carcinoma of the Head and Neck

Saloura

Cho

Kiyotani

et al. 2015

Molecular Cancer Research

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“…Although NEKs have divergent functions, a common feature is their regulation of microtubules (reviewed in Moniz et al [171]). NEK genes have roles in cell cycle regulation as well as ciliagenesis, and it is thought that expansion in organisms with cilia/flagella might be due to the need to coordinate the cell cycle with cilia development [171,172]. In G. lamblia, the NEK family has expanded to an astounding 198 of the 278 protein kinases, 70 per cent of which are likely to be catalytically inactive [37].…”

Section: Gsk3mentioning

confidence: 99%

Diversity, classification and function of the plant protein kinase superfamily

Lehti-Shiu

Shiu

2012

Phil. Trans. R. Soc. B

297

374

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Eukaryotic protein kinases belong to a large superfamily with hundreds to thousands of copies and are components of essentially all cellular functions. The goals of this study are to classify protein kinases from 25 plant species and to assess their evolutionary history in conjunction with consideration of their molecular functions. The protein kinase superfamily has expanded in the flowering plant lineage, in part through recent duplications. As a result, the flowering plant protein kinase repertoire, or kinome, is in general significantly larger than other eukaryotes, ranging in size from 600 to 2500 members. This large variation in kinome size is mainly due to the expansion and contraction of a few families, particularly the receptor-like kinase/Pelle family. A number of protein kinases reside in highly conserved, low copy number families and often play broadly conserved regulatory roles in metabolism and cell division, although functions of plant homologues have often diverged from their metazoan counterparts. Members of expanded plant kinase families often have roles in plant-specific processes and some may have contributed to adaptive evolution. Nonetheless, non-adaptive explanations, such as kinase duplicate subfunctionalization and insufficient time for pseudogenization, may also contribute to the large number of seemingly functional protein kinases in plants.

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“…Mutations of NEK family members have also been identified as drivers behind the development of ciliopathies and cancer. Recent emergence of comprehensive cancer genomes is highlighting certain members of the NEK family as targets of frequent mutations (Moniz, Dutt, Haider, & Stambolic, 2011). We also identified five genes in the RNF family: RNF12, RNF181, RNF20, RNF31,RNF7.…”

Section: Prognostic Gene Identificationmentioning

confidence: 94%

Identification of Biomarkers for Predicting the Overall Survival of Ovarian Cancer Patients: a Sparse Group Lasso Approach

Mai¹,

Zhang²

2016

IJSP

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Next-generation sequencing has been routinely applied to cancer biology, making it possible for researchers to elucidate the molecular mechanisms underlying cancer initiation and progression. However, how to identify oncomarkers from massive complex genomic data poses a great challenge for both modeling and computing. In this paper, we propose a novel computational pipeline to identify genes related to the overall survival of ovarian cancer patients from the rich Cancer Genome Atlas data. Different from the existing studies, we incorporate dependence structure among genes and pathway information into the variable selection. Firstly, the dimensionality of the ovarian cancer data is reduced by a novel stepwise feature screening which mimics the hierarchy of the underlying causal network. The second step of the pipeline is to divide genes into clusters with distinct cellular functions by k-means, x-means and PAMSAM learning algorithms. In the final step, we fit a cox proportional hazard model with a sparse group lasso penalty for further variable selection. Of the 115 genes in the final list, many were reported to be associated with cancer initiation or progression in the literature. In addition, we find several gene families including the NEK family and RNF family, which are closely associated with the survival of ovarian cancer patients.

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Nek family of kinases in cell cycle, checkpoint control and cancer

Cited by 117 publications

References 86 publications

WHSC1 Promotes Oncogenesis through Regulation of NIMA-Related Kinase-7 in Squamous Cell Carcinoma of the Head and Neck

WHSC1 Promotes Oncogenesis through Regulation of NIMA-Related Kinase-7 in Squamous Cell Carcinoma of the Head and Neck

Diversity, classification and function of the plant protein kinase superfamily

Identification of Biomarkers for Predicting the Overall Survival of Ovarian Cancer Patients: a Sparse Group Lasso Approach

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