NEK kinases in cell cycle regulation, DNA damage response, and cancer progression

被引:2
作者
Folahan, Joy T. [1 ]
Barabutis, Nektarios [1 ]
机构
[1] Univ Louisiana Monroe, Coll Pharm, Sch Basic Pharmaceut & Toxicol Sci, 1800 Bienville Dr, Monroe, LA 71201 USA
基金
美国国家卫生研究院;
关键词
Mitosis; Replication stress; Genomic instability; NIMA-RELATED KINASES; PROTEIN-KINASE; MITOCHONDRIAL DYSFUNCTION; CHECKPOINT CONTROL; SPINDLE FORMATION; BETA-CATENIN; MITOSIS GENE; REPLICATION; PHOSPHORYLATION; ACTIVATION;
D O I
10.1016/j.tice.2025.102811
中图分类号
R602 [外科病理学、解剖学]; R32 [人体形态学];
学科分类号
100101 ;
摘要
The NIMA-related kinase (NEK) family of serine/threonine kinases is essential for the regulation of cell cycle progression, mitotic spindle assembly, and genomic stability. In this review, we explore the structural and functional diversity of NEK kinases, highlighting their roles in both canonical and non-canonical cellular processes. We examine recent preclinical findings on NEK inhibition, showcasing promising results for NEK-targeted therapies, particularly in cancer types characterized by high NEK expression. We discussed the therapeutic potential of targeting NEKs as modulators of cell cycle and DDR pathways, with a focus on identifying strategies to exploit NEK activity for enhanced treatment efficacy. Future research directions are proposed to further elucidate NEK-mediated mechanisms and to develop selective inhibitors that target NEK-related pathways.
引用
收藏
页数:11
相关论文
共 208 条
[1]   p21 in cancer: intricate networks and multiple activities [J].
Abbas, Tarek ;
Dutta, Anindya .
NATURE REVIEWS CANCER, 2009, 9 (06) :400-414
[2]   NEK8 regulates DNA damage-induced RAD51 foci formation and replication fork protection [J].
Abeyta, Antonio ;
Castella, Maria ;
Jacquemont, Celine ;
Taniguchi, Toshiyasu .
CELL CYCLE, 2017, 16 (04) :335-347
[3]   DNA damage response revisited: the p53 family and its regulators provide endless cancer therapy opportunities [J].
Abuetabh, Yasser ;
Wu, H. Helena ;
Chai, Chengsen ;
Al Yousef, Habib ;
Persad, Sujata ;
Sergi, Consolato M. ;
Leng, Roger .
EXPERIMENTAL AND MOLECULAR MEDICINE, 2022, 54 (10) :1658-1669
[4]   Mitotic phosphorylation by NEK6 and NEK7 reduces the microtubule affinity of EML4 to promote chromosome congression [J].
Adib, Rozita ;
Montgomery, Jessica M. ;
Atherton, Joseph ;
O'Regan, Laura ;
Richards, Mark W. ;
Straatman, Kees R. ;
Roth, Daniel ;
Straube, Anne ;
Bayliss, Richard ;
Moores, Carolyn A. ;
Fry, Andrew M. .
SCIENCE SIGNALING, 2019, 12 (594)
[5]   Uncovering Cell Cycle Dysregulations and Associated Mechanisms in Cancer and Neurodegenerative Disorders: A Glimpse of Hope for Repurposed Drugs [J].
Advani, Dia ;
Kumar, Pravir .
MOLECULAR NEUROBIOLOGY, 2024, 61 (11) :8600-8630
[6]   Structure of the γ-tubulin ring complex-capped microtubule [J].
Aher, Amol ;
Urnavicius, Linas ;
Xue, Allen ;
Neselu, Kasahun ;
Kapoor, Tarun M. .
NATURE STRUCTURAL & MOLECULAR BIOLOGY, 2024, 31 (07) :1124-1133
[7]   Suppression of reactive oxygen species in endothelial cells by an antagonist of growth hormone-releasing hormone [J].
Akhter, Mohammad S. ;
Barabutis, Nektarios .
JOURNAL OF BIOCHEMICAL AND MOLECULAR TOXICOLOGY, 2021, 35 (10)
[8]   Potential Prognostic Biomarkers of NIMA (Never in Mitosis, Gene A)-Related Kinase (NEK) Family Members in Breast Cancer [J].
Anuraga, Gangga ;
Wang, Wei-Jan ;
Phan, Nam Nhut ;
An Ton, Nu Thuy ;
Ta, Hoang Dang Khoa ;
Berenice Prayugo, Fidelia ;
Minh Xuan, Do Thi ;
Ku, Su-Chi ;
Wu, Yung-Fu ;
Andriani, Vivin ;
Athoillah, Muhammad ;
Lee, Kuen-Haur ;
Wang, Chih-Yang .
JOURNAL OF PERSONALIZED MEDICINE, 2021, 11 (11)
[9]   Murine NIMA-related kinases are expressed in patterns suggesting distinct functions in gametogenesis and a role in the nervous system [J].
Arama, E ;
Yanai, A ;
Kilfin, G ;
Bernstein, A ;
Motro, B .
ONCOGENE, 1998, 16 (14) :1813-1823
[10]   The prolactin receptor scaffolds Janus kinase 2 via co-structure formation with phosphoinositide-4,5-bisphosphate [J].
Araya-Secchi, Raul ;
Bugge, Katrine ;
Seiffert, Pernille ;
Petry, Amalie ;
Haxholm, Gitte W. ;
Lindorff-Larsen, Kresten ;
Pedersen, Stine Falsig ;
Arleth, Lise ;
Kragelund, Birthe B. .
ELIFE, 2023, 12