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Hec1/Nek2
Never in Mitosis (NIMA) Related Kinases (NEKs) are a family of serine/threonine kinases that have a broadly structural similarity to the mitotic regulator NIMA of the filamentous fungus Aspergillus nidulans. The human NEK2 gene is located on the long arm of chromosome 1(1q32.2-1q41) and it is comprised of 8 exons. With the alternate splicing, NEK2 is expressed as three splice variants, namely NEK2A, NEK2B and NEK2C.NEK2 operates a faithful kinetochore microtubule attachments by phosphorylation of highly expressed in cancer 1 (Hec1). NEK2 is well recognized as a multifunctional protein with roles in cell cycle regulation, such as centrosome duplication and separation, microtubule stabilization, kinetochore attachment and spindle assembly checkpoint.
NEK2 phosphorylates Hec1 at Ser165, which is essential for faithful kinetochore microtubule attachments and successful chromosome alignment in mitosis.The expression of NEK2 exhibits a cell cycle-dependent pattern, which is low in G1 phase, peaking in S and G2 phase. Several proteins have been demonstrated as transcriptional repressors of NEK2. Chromatin immunoprecipitation (ChIP) assay demonstrated that the E2F4, a member of the E2F transcription factor family, binds to the promoter of NEK2 in early G1. Besides the transcriptional regulation, the cellular NEK2 abundance is also mediated by the ubiquitin-proteasome system (UPS). The catalytic domain of NEK2 is phosphorylated and activated by p90RSK2, an effector of the MAPK pathway, which is important for the chromatin Cell Cycle condensation in mouse spermatocytes.
References
1.Fang, Y,et al. Cell Cycle, 15(7), 895–907.
NEK2 phosphorylates Hec1 at Ser165, which is essential for faithful kinetochore microtubule attachments and successful chromosome alignment in mitosis.The expression of NEK2 exhibits a cell cycle-dependent pattern, which is low in G1 phase, peaking in S and G2 phase. Several proteins have been demonstrated as transcriptional repressors of NEK2. Chromatin immunoprecipitation (ChIP) assay demonstrated that the E2F4, a member of the E2F transcription factor family, binds to the promoter of NEK2 in early G1. Besides the transcriptional regulation, the cellular NEK2 abundance is also mediated by the ubiquitin-proteasome system (UPS). The catalytic domain of NEK2 is phosphorylated and activated by p90RSK2, an effector of the MAPK pathway, which is important for the chromatin Cell Cycle condensation in mouse spermatocytes.
References
1.Fang, Y,et al. Cell Cycle, 15(7), 895–907.
Cell Cycle/DNA Damage
ABC(12)
AChR(42)
Antifolate(10)
ATM/ATR(24)
Aurora Kinase(46)
CLK(15)
c-Myc(22)
DHFR(7)
DNA Alkylator(33)
DNA gyrase(10)
DNA Repair Protein(21)
DNA/RNA Synthesis(141)
DNA-PK(13)
GPR(66)
HDAC(138)
Hec1/Nek2(9)
Integrin(55)
LIM Kinase (LIMK)(7)
Mps1/TTK(2)
Nucleoside Antimetabolite/Analog(48)
Other Targets(4)
PAK(11)
PARP(50)
PLK(19)
Potassium Channel(107)
RAD51(1)
Rho(10)
ROCK(29)
Telomerase(9)
Topoisomerase(61)
Wee1(4)
