GINS complex protein Sld5 recruits SIK1 to activate MCM helicase during DNA replication

Joshi, Kiranmai; Shah, Varun; Maddika, Subbareddy

doi:10.1016/j.cellsig.2016.08.018

Cited by 12 publications

(17 citation statements)

References 26 publications

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“…M1 is highly conserved among influenza A and B viruses. It has been reported that SLD5 interacts with Psf1, Psf2, and Psf3 (Choi et al, 2007;Gouge & Christensen, 2010;Joshi et al, 2016;Takayama et al, 2003). We found that M1 blocks host cell DNA replication likely by interacting with SLD5 to disrupt the normal function of the GINS complex.…”

Section: Discussionmentioning

confidence: 56%

“…First, knockdown or mutation of SLD5 (△7aa) in cells resulted in delayed cell cycle progress. It has been reported that SLD5 interacts with Psf1, Psf2, and Psf3 (Choi et al, 2007;Gouge & Christensen, 2010;Joshi et al, 2016;Takayama et al, 2003). The SLD5△7aa mutant failed to bind Psf2, which might Inhibiting host replication provides an advantage during virus life cycle by reducing or eliminating competing host macromolecular synthesis (Chen & Makino, 2004;Flemington, 2001).…”

Section: Discussionmentioning

confidence: 99%

“…The △7aa mutant showed a band migrating with a faster electrophoretic mobility compared with wild-type SLD5 protein by western blot (Figure 3h). Previous studies indicated that within the GINS complex, SLD5 interacts with Psf1, Psf2, and Psf3 (Gouge & Christensen, 2010;Joshi, Shah, & Maddika, 2016;Takayama et al, 2003). Thus, we further characterised the binding properties of △7aa mutant.…”

Section: Sld5 Suppresses Influenza Virus Replicationmentioning

confidence: 93%

“…control vector or SLD5 were also established and the high expression level of SLD5 protein in the SLD5-transfected 293T cell line was confirmed by western blot(Figure 3c). Previous studies indicated that within the GINS complex, SLD5 interacts with Psf1, Psf2, and Psf3(Gouge & Christensen, 2010;Joshi, Shah, & Maddika, 2016;Takayama et al, 2003). We next knocked down SLD5 in A549 by using two SLD5 specific siRNA and used a nontargeting siRNA as negative control.…”

mentioning

confidence: 99%

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Influenza virus matrix protein M1 interacts with SLD5 to block host cell cycle

Zhu

Zhao

et al. 2019

Cellular Microbiology

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Influenza virus matrix 1 protein (M1) is highly conserved and plays essential roles at many stages of virus life cycle. Here, we used a yeast two-hybrid system to identify the host protein SLD5, a component of the GINS complex, which is essential for the initiation of DNA replication in eukaryotic cells, as a new M1 interacting protein. M1 from several different influenza virus strains all interacted with SLD5. Overexpression of SLD5 suppressed influenza virus replication. Transient, stable, or inducible expression of M1 induced host cell cycle blockade at G0/G1 phase. Moreover, SLD5 partially rescued M1 expression-or influenza virus infection-induced G0/G1 phase accumulation in cell lines and primary mouse embryonic fibroblasts. Importantly, SLD5 transgenic mice exhibited higher resistance and improved lung epithelial regeneration after virus infection compared with wild-type mice. Therefore, influenza virus M1 blocks host cell cycle process by interacting with SLD5. Our finding reveals the multifunctional nature of M1 and provides new insight for understanding influenza virus-host interaction.

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Section: Discussionmentioning

confidence: 56%

Section: Discussionmentioning

confidence: 99%

Section: Sld5 Suppresses Influenza Virus Replicationmentioning

confidence: 93%

mentioning

confidence: 99%

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Influenza virus matrix protein M1 interacts with SLD5 to block host cell cycle

Zhu

Zhao

et al. 2019

Cellular Microbiology

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“…In addition to MCM7, MCM2 was shown to be a substrate of salt-induciblekinase1 (SIK1) [ 66 ], MCM3 was reported to be phosphorylated by death-associated protein kinase (DAPK) at Ser-160 [ 67 ], and MCM4 was phosphorylated by Epstein–Barr virus-encoded protein kinase (EBV-PK) at Thr-19 and Thr-110 [ 31 ]. Among these, SIK1-dependent MCM2 phosphorylation, mediated by Sld5, is required for MCM helicase activity, but it does not affect the chromatin association of MCM2 [ 66 ]. The authors identified five SIK1-dependent phosphosites on MCM2 in vitro; however, specific phosphosites in cells need further identification.…”

Section: Phosphorylation Of Mcms By Other Kinasesmentioning

confidence: 99%

Role of MCM2–7 protein phosphorylation in human cancer cells

Fei

2018

Cell Biosci

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A heterohexameric complex composed of minichromosome maintenance protein 2–7 (MCM2–7), which acts as a key replicative enzyme in eukaryotes, is crucial for initiating DNA synthesis only once per cell cycle. The MCM complex remains inactive through the G1 phase, until the S phase, when it is activated to initiate replication. During the transition from the G1 to S phase, the MCM undergoes multisite phosphorylation, an important change that promotes subsequent assembly of other replisome members. Phosphorylation is crucial for the regulation of MCM activity and function. MCMs can be phosphorylated by multiple kinases and these phosphorylation events are involved not only in DNA replication but also cell cycle progression and checkpoint response. Dysfunctional phosphorylation of MCMs appears to correlate with the occurrence and development of cancers. In this review, we summarize the currently available data regarding the regulatory mechanisms and functional consequences of MCM phosphorylation and seek the probability that protein kinase inhibitor can be used therapeutically to target MCM phosphorylation in cancer.

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The molecular circadian rhythms regulating the cell cycle

Zhou,

Wang,

et al. 2024

J of Cellular Biochemistry

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The circadian clock controls the expression of a large proportion of protein‐coding genes in mammals and can modulate a wide range of physiological processes. Recent studies have demonstrated that disruption or dysregulation of the circadian clock is involved in the development and progression of several diseases, including cancer. The cell cycle is considered to be the fundamental process related to cancer. Accumulating evidence suggests that the circadian clock can control the expression of a large number of genes related to the cell cycle. This article reviews the mechanism of cell cycle‐related genes whose chromatin regulatory elements are rhythmically occupied by core circadian clock transcription factors, while their RNAs are rhythmically expressed. This article further reviews the identified oscillatory cell cycle‐related genes in higher organisms such as baboons and humans. The potential functions of these identified genes in regulating cell cycle progression are also discussed. Understanding how the molecular clock controls the expression of cell cycle genes will be beneficial for combating and treating cancer.

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GINS complex protein Sld5 recruits SIK1 to activate MCM helicase during DNA replication

Cited by 12 publications

References 26 publications

Influenza virus matrix protein M1 interacts with SLD5 to block host cell cycle

Influenza virus matrix protein M1 interacts with SLD5 to block host cell cycle

Role of MCM2–7 protein phosphorylation in human cancer cells

The molecular circadian rhythms regulating the cell cycle

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