Journal: Cell Death & Disease

Article Title: Pyruvate kinase L/R links metabolism dysfunction to neuroendocrine differentiation of prostate cancer by ZBTB10 deficiency

doi: 10.1038/s41419-022-04694-z

Figure Lengend Snippet: A , B IHC staining of PKLR and ZBTB10 on consecutive sections of a PCa TMA (CA4) in two selected cases. Scale bars, 100 μm. C Correlation analysis of the intensities of PKLR and ZBTB10 of the PCa TMA ( n = 49). PKLR expression was negatively associated with ZBTB10-expressing PCa samples. R , correlation coefficient; p , two-tailed p value. Significance was determined by correlation XY analyses in GraphPad Prism. D , E Tumor grade association analysis using a Chi-squared test of the CA9 PCa TMA. Intensities of PKLR ( D ) and ZBTB10 ( E ) staining were semiquantitatively scored using the H-index as follows: negative, weakly positive, moderately positive, and strongly positive. p values were calculated by a Chi-squared test performed using SPSS statistical 18.0 software. p < 0.001. F Proposed model for ADT-induced PKLR drives hormone-refractory PCa. Hormone-sensitive PCa activates AR signaling by increasing ZBTB10 leading to increased binding to the PKLR regulatory sequence and mediation of its transcriptional suppression. ADT induced inactivation of the AR-ZBTB10 pathway, leading to an abundance of PKLR through ZBTB10 loss of function. Overexpression of PKLR may upregulate glucose metabolism and NED progression of PCa cells. Targeting PKLR by potential PKLR inhibitors may reduce the PKLR-driven glycolysis and NED of ADT-resistant PCa.

Article Snippet: To mimic ADT, cells were cultured in RPMI-1640 medium with 5% CSS (ThermoFisher, 12676-029)-containing medium for 48 h or treated with 10 μM MDV3100 (Selleckchem, S1250) under standard culture conditions for 48 h. The AR ligand was treated with 10 nM DHT (Sigma-Aldrich) for 24 h. The candidate PKLR inhibitors (vilanterol, saquinavir, fosinopril, and salmeterol) were purchased from MedChemExpress (HY-14300, HY-17007, HY-B0382, and HY-14302), and the concentrations of each candidate drug for cell viability were treated with 0, 1, 5, 10, 25, and 50 μM for 24 h.

Techniques: Immunohistochemistry, Expressing, Two Tailed Test, Staining, Software, Binding Assay, Sequencing, Over Expression

Journal: The Journal of Biological Chemistry

Article Title: Structure and Evolution of the Archaeal Lipid Synthesis Enzyme sn -Glycerol-1-phosphate Dehydrogenase *

doi: 10.1074/jbc.M115.647461

Figure Lengend Snippet: Expanded gap version of Dali-lite pairwise structural alignment of MJ G1PDH (36). Selected members of the larger enzyme superfamily including GDHs (Protein Data Bank codes 3CE9 and 1JQ5), ADHs (Protein Data Bank codes 1RRM, 3JZD, 3BFJ, and 4FR2), and DHQSs (Protein Data Bank codes 3QBE, 1XAG, and 1UJN) were used in the alignment. Secondary structural elements and residue numbering correspond to G1PDH. Residues that coordinate metals are highlighted in blue. The coenzyme binding motif is in italics, whereas residues that interact with coenzyme (NADP(H)) and substrate (DHAP) with respect to MJ G1PDH are highlighted in yellow and green, respectively. Reported intersubunit contacts between monomers are in red. Uppercase lettering indicates structurally equivalent positions with G1PDH, whereas lowercase indicates insertions relative to G1PDH.

Article Snippet: Previous biochemical characterizations of archaeal G1PDHs have shown the enzyme to be multimeric ( 17 , 42 ). table ft1 table-wrap mode="anchored" t5 TABLE 3 caption a7 Organism Class Protein Data Bank code-monomer Z-score a r.m.s.d. b lali c %id d C. acetobutylicum ATCC 824 GDH 3CE9-A 39.1 2.0 310 34 Sinorhizobium meliloti GDH 3UHJ-A 31.7 2.6 305 21 Geobacillus stearothermophilus GDH 1JQ5-A 30.3 2.5 300 21 Serratia plymuthica A30 GDH 4MCA-A 30.1 2.7 302 21 Schizosaccharomyces pombe GDH 1TA9-B 29.7 2.7 306 20 T. maritima GDH 1KQ3-A 29.5 2.6 301 26 E. coli Lactaldehyde reductase 1RRM-A 27.2 3.1 301 16 Ralstonia eutropha Fe-ADH 3JZD-A 26.9 2.9 302 15 Rhizobium sp. MTP-10005 MR 3W5S-A 26.8 3.2 300 15 Klebsiella pneumoniae POR 3BFJ-A 26.7 3.1 302 18 Agrobacterium tumefaciens MR 3HL0-A 26.8 3.0 302 15 Zymomonas mobilis ADH 2 3OWO-A 26.4 3.2 302 16 O. oeni POR 4FR2-A 26.4 3.2 302 20 Corynebacterium glutamicum ADH IV 3IV7-A 26.0 3.1 303 16 T. maritima Butanol dehydrogenase 1VLJ-B 25.2 3.5 299 18 T. maritima Fe-ADH 1VHD-A 25.1 3.2 294 18 Geobacillus thermoglucosidasius ADH 3ZDR-A 24.2 3.2 299 16 Shewanella denitrificans Fe-ADH 3RF7-A 24.2 3.4 290 17 E. coli Hypothetical oxidoreductase YqhD 1OJ7-A 23.6 3.9 300 17 Actinidia chinensis DHQS 3ZOK-D 23.0 3.5 294 16 Mycobacterium tuberculosis DHQS 3QBE-A 22.9 2.9 287 14 Aspergillus nidulans DHQS 1NVB-B 22.3 3.3 290 17 Streptomyces hygroscopicus Cyclase 4P53-A 21.0 2.9 277 16 Staphylococcus aureus DHQS 1XAG-A 20.9 3.3 282 17 Bacillus circulans 2-Deoxy- scyllo -inosose synthase 2GRU-A 20.3 3.2 283 18 Staphylococcus aureus DHQS 1XAH-A 19.5 3.2 264 16 Vibrio cholerae DHQS 3OKF-A 19.4 3.4 280 18 T. thermophilus DHQS 1UJN-A 18.8 3.4 271 14 Helicobacter pylori DHQS 3CLH-A 17.6 3.4 255 21 Open in a separate window a A measure of the statistical significance of the result relative to an alignment of random structures. b Root mean square deviation of α-carbon atoms. c Number of aligned residues. d Sequence identity between the two chains.

Techniques: Binding Assay

Journal: The Journal of Biological Chemistry

Article Title: Structure and Evolution of the Archaeal Lipid Synthesis Enzyme sn -Glycerol-1-phosphate Dehydrogenase *

doi: 10.1074/jbc.M115.647461

Figure Lengend Snippet: Top structural alignment hits from the Dali-based structural alignment of MJ G1PDH ( 36 ) MR, maleylacetate reductase; POR, 1,3-propanediol oxidoreductase.

Article Snippet: Previous biochemical characterizations of archaeal G1PDHs have shown the enzyme to be multimeric ( 17 , 42 ). table ft1 table-wrap mode="anchored" t5 TABLE 3 caption a7 Organism Class Protein Data Bank code-monomer Z-score a r.m.s.d. b lali c %id d C. acetobutylicum ATCC 824 GDH 3CE9-A 39.1 2.0 310 34 Sinorhizobium meliloti GDH 3UHJ-A 31.7 2.6 305 21 Geobacillus stearothermophilus GDH 1JQ5-A 30.3 2.5 300 21 Serratia plymuthica A30 GDH 4MCA-A 30.1 2.7 302 21 Schizosaccharomyces pombe GDH 1TA9-B 29.7 2.7 306 20 T. maritima GDH 1KQ3-A 29.5 2.6 301 26 E. coli Lactaldehyde reductase 1RRM-A 27.2 3.1 301 16 Ralstonia eutropha Fe-ADH 3JZD-A 26.9 2.9 302 15 Rhizobium sp. MTP-10005 MR 3W5S-A 26.8 3.2 300 15 Klebsiella pneumoniae POR 3BFJ-A 26.7 3.1 302 18 Agrobacterium tumefaciens MR 3HL0-A 26.8 3.0 302 15 Zymomonas mobilis ADH 2 3OWO-A 26.4 3.2 302 16 O. oeni POR 4FR2-A 26.4 3.2 302 20 Corynebacterium glutamicum ADH IV 3IV7-A 26.0 3.1 303 16 T. maritima Butanol dehydrogenase 1VLJ-B 25.2 3.5 299 18 T. maritima Fe-ADH 1VHD-A 25.1 3.2 294 18 Geobacillus thermoglucosidasius ADH 3ZDR-A 24.2 3.2 299 16 Shewanella denitrificans Fe-ADH 3RF7-A 24.2 3.4 290 17 E. coli Hypothetical oxidoreductase YqhD 1OJ7-A 23.6 3.9 300 17 Actinidia chinensis DHQS 3ZOK-D 23.0 3.5 294 16 Mycobacterium tuberculosis DHQS 3QBE-A 22.9 2.9 287 14 Aspergillus nidulans DHQS 1NVB-B 22.3 3.3 290 17 Streptomyces hygroscopicus Cyclase 4P53-A 21.0 2.9 277 16 Staphylococcus aureus DHQS 1XAG-A 20.9 3.3 282 17 Bacillus circulans 2-Deoxy- scyllo -inosose synthase 2GRU-A 20.3 3.2 283 18 Staphylococcus aureus DHQS 1XAH-A 19.5 3.2 264 16 Vibrio cholerae DHQS 3OKF-A 19.4 3.4 280 18 T. thermophilus DHQS 1UJN-A 18.8 3.4 271 14 Helicobacter pylori DHQS 3CLH-A 17.6 3.4 255 21 Open in a separate window a A measure of the statistical significance of the result relative to an alignment of random structures. b Root mean square deviation of α-carbon atoms. c Number of aligned residues. d Sequence identity between the two chains.

Techniques:

Journal: Developmental biology

Article Title: Identification of regulators of germ stem cell enwrapment by its niche in C. elegans

doi: 10.1016/j.ydbio.2017.06.019

Figure Lengend Snippet: Genes required for DTC plexus formation in the L3/L4 stage.

Article Snippet: Scale bar, 10 μm. table ft1 table-wrap mode="anchored" t5 caption a7 Gene Public Name (Reference) Sequence Name (Gene) CDS Description DTC Plexus Defect PercentC Defect Tissue-specific RNAi Site of Action Mitochondria and energy metabolism nuo-1 C09H10.3 NADH ubiquinone oxidoreductase 7/11 64% DTC let-754 C29E4.8 Adenylate kinase 4/16 25% DTC, GCs C16A3.5 C16A3.5 NADH:ubiquinone oxidoreductase 4/20 20% DTC rpom-1 Y105E8A.23 Mitochondrial RNA polymerase 4/20 20% dld-1 LLC1.3 Dihydrolipoamide dehydrogenase 3/19 16% GCs Transport and vesicle trafficking sec-10 C33H5.9 Exocyst subunit 7/18 39% DTC emo-1 F32D8.6 Sec61p gamma subunit 4/15 27% DTC, GCs copa-1 Y71F9AL.17 COPI complex alpha subunit 3/9 33% DTC, GCs sar-1 ZK180.4 SAR (Secretion Associated, Ras-related) COPII vesicle coat protein 3/19 16% dyn-1 C02C6.1 Dynamin GTPase 5/24 21% RNA Regulation rnp-7 K04G7.10 RNP (RRM RNA binding domain)-containing 4/20 20% DTC snr-2 W08E3.1 Small nuclear ribonucleoprotei n polypeptide 3/16 19% GCs Protein Synthesis and Degradation dre-1 K04A8.6 F-box domain-containing protein 9/29 31% GCs hars-1 T11G6.1 Histidyl tRNA synthetase 8/10 80% DTC rpl-11.1 T22F3.4 Large ribosomal subunit L11 5/17 29% F23B12.7 F23B12.7 Constituent of 66S pre-ribosomal particles 7/19 37% W07E6.2 W07E6.2 WD-repeat protein RSA4/Notchless 4/26 15% GCs ppp-1 C15F1.4 Translation initiation factor eIF2B gamma subunit 3/19 16% uba-1 C47E12.5 Ubiquitin-activating enzyme 6/18 33% GCs Chromatin and transcription lin-40 T27C4.4 Histone deacetylase complex, chromatin binding 9/19 47% DTC pab-1 Y106G6H.2 Poly(A)-binding protein 7/29 24% DTC, GCs his-72 Y49E10.6 H3 histone 3/20 15% GCs Cell signaling clr-1 F56D1.4 Receptor tyrosine phosphatase 5/21 24% sur-6 F26E4.1 Regulatory subunit of serine/ threonine protein phosphatase 2A 3/19 16% lin-3 F36H1.4 EGF family ligand 4/27 15% Nuclear Transport and signaling ran-1 K01G5.4 Ran GTPase 5/15 33% DTC, GCs ftt-2/par-5 a F52D10.3 14-3-3 signaling and scaffolding protein 5/18 28% DTC ( ftt-2 ), GCs ( par-5 ) Focal adhesion unc-112 C47E8.7 Fermitin, PH domain-containing protein 9/17 53% DTC Uncharacterized nematode-specific gene R08C7.1 R08C7.1 Protein coding gene 6/25 24% DTC, GCs Open in a separate window Genes are grouped by reported function or predicted function based on homologs.

Techniques: Sequencing, RNA Binding Assay, Ubiquitin Proteomics, Histone Deacetylase Assay, Binding Assay, Scaffolding