Vigilin protein Vgl1 is required for heterochromatin-mediated gene silencing in Schizosaccharomyces pombe

Farooq, Zeenat; Abdullah, Ehsaan; Banday, Shahid; Ganai, Shabir Ahmad; Rashid, Romana; Mushtaq, Arjamand; Rashid, Sabrina Mohd; Altaf, Mohammad

doi:10.1074/jbc.ra119.009262

Cited by 8 publications

(4 citation statements)

References 66 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Vgl1 mutants in S. pombe lose their viability at high temperature, showing that Vgl1 mediates cell survival under thermal stress (24). In addition, Vgl1 is required for doxorubicin resistance in the fission yeast S. pombe (36) and is required for heterochromatin integrity (37).…”

Section: Discussionmentioning

confidence: 99%

TSC2 Interacts with HDLBP/Vigilin and Regulates Stress Granule Formation

Kosmas

Filippakis

Khabibullin

et al. 2021

Molecular Cancer Research

View full text Add to dashboard Cite

Tuberous sclerosis complex (TSC) is caused by mutations of either the TSC1 or TSC2 tumor suppressor gene. TSC causes tumors of the brain, heart, kidney, skin and lymphangioleiomyomatosis (LAM). Here we report that the TSC2 protein physically binds to high-density lipoprotein binding protein (HDLBP), also called vigilin, a core stress granule (SG) protein, and that TSC2 localizes to SGs. SGs contain mRNAs and translation initiation complexes, and regulate gene expression by sequestering specific transcripts, thereby serving a cytoprotective role. TSC2 has never before been shown to localize to SGs and knocking down vigilin impacts SG translocation of TSC2. TSC2-deficient cells showed a striking increase in the number of SGs after thermal shock and arsenite treatment relative to Tsc2-expressing cells. Our findings also show that murine kidney lysates from a model of TSC have increased levels of SG components including G3BP1 and Caprin1. G3BP1 and Caprin are elevated in renal angiomyolipomas (a renal tumor common in patients with TSC) compared with control normal kidney. G3BP1 is also elevated in TSC-associated subependymal giant cell astrocytomas. We found that genetic inhibition of G3BP1 inhibits the proliferation of TSC2-deficient cells in vitro. Finally, in a mouse model of TSC, genetic inhibition of SGs suppresses cell growth, suggesting that targeting SGs may have efficacy in the therapy of TSC. Implications: This study demonstrates that TSC2 physically interacts with HDLBP/vigilin, a component of SGs, that TSC2 localizes to SG and that TSC2-deficient cells have more SGs, suggesting that SGs represent a novel therapeutic target in TSC.

show abstract

Section: Discussionmentioning

confidence: 99%

TSC2 Interacts with HDLBP/Vigilin and Regulates Stress Granule Formation

Kosmas

Filippakis

Khabibullin

et al. 2021

Molecular Cancer Research

View full text Add to dashboard Cite

show abstract

“…Besides the defined functions, GalaxyRefine performs structural relaxation through its molecular dynamic simulations [ 49 ]. The GalaxyRefine models show improvement both in local as well as in global structure quality, which is seen, especially when the models to be refined have been generated through modeling software’s based on futuristic or advanced algorithms [ 49 , 50 ].…”

Section: Methodsmentioning

confidence: 99%

Biochemical Characterization and Functional Analysis of Heat Stable High Potential Protease of Bacillus amyloliquefaciens Strain HM48 from Soils of Dachigam National Park in Kashmir Himalaya

et al. 2021

Self Cite

View full text Add to dashboard Cite

A novel temperature stable alkaline protease yielding bacteria was isolated from the soils of Dachigam National Park, which is known to be inhabited by a wide variety of endemic plant and animal species of Western Himalaya. This high-potential protease producing isolate was characterized and identified as Bacillus amyloliquefaciens strain HM48 by morphological, Gram’s staining and biochemical techniques followed by molecular characterization using 16S rRNA approach. The extracellular protease of B. amyloliquefaciens HM48 was purified by precipitating with ammonium sulfate (80%), followed by dialysis and Gel filtration chromatography increasing its purity by 5.8-fold. The SDS–PAGE analysis of the purified enzyme confirmed a molecular weight of about ≈25 kDa. The enzyme displayed exceptional activity in a broad temperature range (10–90 °C) at pH 8.0, retaining its maximum at 70 °C, being the highest reported for this proteolytic Bacillus sp., with KM and Vmax of 11.71 mg/mL and 357.14 µmol/mL/min, respectively. The enzyme exhibited remarkable activity and stability against various metal ions, surfactants, oxidizing agent (H2O2), organic solvents and displayed outstanding compatibility with widely used detergents. This protease showed effective wash performance by exemplifying complete blood and egg-yolk stains removal at 70 °C and efficiently disintegrated chicken feathers making it of vital importance for laundry purpose and waste management. For functional analysis, protease gene amplification of strain HM48 yielded a nucleotide sequence of about 700 bp, which, when checked against the available sequences in NCBI, displayed similarity with subtilisin-like serine protease of B. amyloliquefaciens. The structure of this protease and its highest-priority substrate β-casein was generated through protein modeling. These protein models were validated through futuristic algorithms following which protein–protein (protease from HM48 and β-casein) docking was performed. The interaction profile of these proteins in the docked state with each other was also generated, shedding light on their finer details. Such attributes make this thermally stable protease novel and suitable for high-temperature industrial and environmental applications.

show abstract

“…The posttranslational H3K9me3 modification is thought to be a heterochromatin marker which causes the transcriptional repression of local genes in S. pombe (Akoury et al, 2019 ; Farooq et al, 2019 ), but the physiological roles of H3K9me3 in T. reesei remain elusive. To identify the T. reesei H3K9 methyltransferase and investigate its biological functions, a homologous gene, Trire2_111216 (hereafter named TrDIM5) , was found by searching the T. reesei genome ( https://mycocosm.jgi.doe.gov/Trire2/Trire2.home.html ) using Sp Clr4, (GenBank: CAA22283.1) as a query.…”

Section: Resultsmentioning

confidence: 99%

Section: Identification Of the Spclr4 Orthologue In T Reeseimentioning

confidence: 99%

A histone H3K9 methyltransferase Dim5 mediates repression of sorbicillinoid biosynthesis in Trichoderma reesei

Wang

Liu

et al. 2022

Microbial Biotechnology

View full text Add to dashboard Cite

Sorbicillinoids (also termed yellow pigment) are derived from either marine or terrestrial fungi, exhibit various biological activities and therefore show potential as commercial products for human or animal health. The cellulolytic filamentous fungus Trichoderma reesei is capable to biosynthesize sorbicillinoids, but the underlying regulatory mechanism is not yet completely clear. Herein, we identified a histone H3 lysine 9 (H3K9) methyltransferase, Dim5, in T. reesei. TrDIM5 deletion caused an impaired vegetative growth as well as conidiation, whereas the ∆Trdim5 strain displayed a remarkable increase in sorbicillinoid production. Post TrDIM5 deletion, the transcription of sorbicillinoid biosynthesis‐related (SOR) genes was significantly upregulated with a more open chromatin structure. Intriguingly, hardly any expression changes occurred amongst those genes located on both flanks of the SOR gene cluster. In addition, the assays provided evidence that H3K9 triple methylation (H3K9me3) modification acted as a repressive marker at the SOR gene cluster and thus directly mediated the repression of sorbicillinoid biosynthesis. Transcription factor Ypr1 activated the SOR gene cluster by antagonizing TrDim5‐mediated repression and therefore contributed to forming a relatively more open local chromatin environment, which further facilitated its binding and SOR gene expression. The results of this study will contribute to understanding the intricate regulatory network in sorbicillinoid biosynthesis and facilitate the endowment of T. reesei with preferred features for sorbicillinoid production by genetic engineering.

show abstract

Vigilin protein Vgl1 is required for heterochromatin-mediated gene silencing in Schizosaccharomyces pombe

Cited by 8 publications

References 66 publications

TSC2 Interacts with HDLBP/Vigilin and Regulates Stress Granule Formation

TSC2 Interacts with HDLBP/Vigilin and Regulates Stress Granule Formation

Biochemical Characterization and Functional Analysis of Heat Stable High Potential Protease of Bacillus amyloliquefaciens Strain HM48 from Soils of Dachigam National Park in Kashmir Himalaya

A histone H3K9 methyltransferase Dim5 mediates repression of sorbicillinoid biosynthesis in Trichoderma reesei

Contact Info

Product

Resources

About