NEK11−Linking CHK1 and CDC25A in DNA damage checkpoint signaling

Sørensen, Claus Storgaard; Melixetian, Marina; Klein, Ditte Kjærsgaard; Helin, Kristian

doi:10.4161/cc.9.3.10513

Cited by 29 publications

(28 citation statements)

References 44 publications

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“…UV-induced activation of ATR leads to the phosphorylation of checkpoint kinase 1 (CHK1) at Ser 345 [47], which subsequently phosphorylates and inhibits CDC25 activity, halting the cell cycle in a manner similar to CHK2 [48]. CHK1 can also inhibit CDC25 activity by either the activation of Never In Mitosis A (NIMA)-Related Kinase 11 (NEK11), which phosphorylates and inhibits CDC25 [49, 50], or via direct inhibition of the polo-like kinase 1 (PLK-1), a known activator of CDC25 [51]. Analogous to the action of ATM, ATR increases p53 stability through phosphorylation of MDM2 at Ser 407 .…”

Section: Dna Damagementioning

confidence: 99%

Molecular signaling cascades involved in nonmelanoma skin carcinogenesis

Feehan

Shantz

2016

Biochemical Journal

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Non-melanoma skin cancer (NMSC) is the most common cancer world-wide and the incidence continues to rise, in part due to increasing numbers in high-risk groups such as organ transplant recipients and those taking photosensitizing medications. The most significant risk factor for NMSC is ultraviolet radiation (UVR) from sunlight, specifically UVB, which is the leading cause of DNA damage, photoaging, and malignant transformation in the skin. Activation of apoptosis following UVR exposure allows the elimination of irreversibly damaged cells that may harbor oncogenic mutations. However, UVR also activates signaling cascades that promote the survival of these potentially cancerous cells, resulting in tumor initiation. Thus, the UVR-induced stress response in the skin is multi-faceted and requires coordinated activation of numerous pathways controlling DNA damage repair, inflammation, and kinase-mediated signal transduction that lead to either cell survival or cell death. This review focuses on the central signaling mechanisms that respond to UVR and the subsequent cellular changes. Given the prevalence of NMSC and the resulting health care burden, many of these pathways provide promising targets for continued study aimed at both chemoprevention and chemotherapy.

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Section: Dna Damagementioning

confidence: 99%

Molecular signaling cascades involved in nonmelanoma skin carcinogenesis

Feehan

Shantz

2016

Biochemical Journal

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“…Like G 1 /S entry, DDR pathway plays a critical role in controlling G 2 /M entry by regulating Cdc25A abundance [82]. It was revealed that activated Chk1 phosphorylates NIMA (never in mitosis gene A)-related kinase 11 (NEK11) at S273 and causes NEK11 activation [83].…”

Section: The Role Of Cdc25a In Regulating Cell Proliferationmentioning

confidence: 99%

The Role of Cdc25A in the Regulation of Cell Proliferation and Apoptosis

Shen¹,

Huang²

2012

ACAMC

165

143

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Cell division cycle 25 A (Cdc25A), a dual-specificity protein phosphatase, is one of the most crucial cell cycle regulators, which removes the inhibitory phosphorylation in cyclin-dependent kinases (CDKs), such as CDK2, CDK4, and CDK6, and positively regulates the activities of CDKs that lead to cell cycle progression. In addition, Cdc25A also acts as a regulator of apoptosis. Overexpression of Cdc25A promotes tumorigenesis, and is frequently observed in various types of cancer. Here we briefly summarize current understanding of the role of Cdc25A in cell proliferation and apoptosis, as well as the impact of overexpression of Cdc25A on tumorigenesis.

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“…In contrast to GSK3β, NEK11 appeared most active in promoting CDC25A degradation in S and G2 phases. NEK11 expression increases during colon cancer progression, suggesting a role in tumorigenesis, and future research is required to confirm this link [31]. Overall, the identification of multiple degron kinases and sequential phoshorylations for CDC25A suggests regulation by multiple signaling pathways, although a consensus, unified model for the fine details of CDC25A degradation has not yet emerged.…”

Section: Scf and Dna Damage-induced Cell Cycle Arrestmentioning

confidence: 99%

SCF ubiquitin ligases in the maintenance of genome stability

Silverman

Skaar

Pagano

2012

Trends in Biochemical Sciences

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In response to genotoxic stress, eukaryotic cells activate the DNA damage response (DDR), a series of pathways that coordinate cell cycle arrest and DNA repair to prevent deleterious mutations. In addition, cells possess checkpoint mechanisms that prevent aneuploidy by regulating the number of centrosomes and the spindle assembly. Among these mechanisms, ubiquitin-mediated degradation of key proteins has an important role in the regulation of the DDR, centrosome duplication and chromosome segregation. This review discusses the functions of a group of ubiquitin ligases, the SCF (SKP1-CUL1-F-box protein) family, in the maintenance of genome stability. Given that general proteasome inhibitors are currently used as anticancer agents, a better understanding of the ubiquitylation of specific targets by specific ubiquitin ligases may result in improved cancer therapeutics.

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NEK11−Linking CHK1 and CDC25A in DNA damage checkpoint signaling

Cited by 29 publications

References 44 publications

Molecular signaling cascades involved in nonmelanoma skin carcinogenesis

Molecular signaling cascades involved in nonmelanoma skin carcinogenesis

The Role of Cdc25A in the Regulation of Cell Proliferation and Apoptosis

SCF ubiquitin ligases in the maintenance of genome stability

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