Faculty Opinions recommendation of HnRNP proteins controlled by c-Myc deregulate pyruvate kinase mRNA splicing in cancer.

AbstractWe have determined the effect of seven serine- and arginine-rich (SR) proteins and 15 heterogenous nuclear ribonucleoproteins (hnRNPs) on human papillomavirus type 16 (HPV16) late gene expression. Of the seven SR proteins analyzed here, SRSF1, SRSF3, and SRSF9 induced HPV16 late gene expression, and five of the SR proteins affected HPV16 L1 mRNA splicing. Of the 15 hnRNP proteins analyzed here, hnRNP A2, hnRNP F, and hnRNP H efficiently induced HPV16 late gene expression, and all of the hnRNPs affected HPV16 L1 mRNA levels or mRNA splicing. Thus, the majority of SR proteins and hnRNPs have the potential to regulate HPV16 L1 mRNA splicing. Strict control of the expression of the immunogenic L1 and L2 capsid proteins may contribute to the ability of HPV16 to cause persistence.

Download Full-text

Concentration-dependent control of pyruvate kinase M mutually exclusive splicing by hnRNP proteins

Nature Structural & Molecular Biology ◽

10.1038/nsmb.2219 ◽

2012 ◽

Vol 19 (3) ◽

pp. 346-354 ◽

Cited By ~ 63

Author(s):

Mo Chen ◽

Charles J David ◽

James L Manley

Keyword(s):

Pyruvate Kinase ◽

Hnrnp Proteins

Download Full-text

Organization of transcription and pre-mRNA splicing within the mammalian cell nucleus

Proceedings, annual meeting, Electron Microscopy Society of America ◽

10.1017/s042482010014021x ◽

1995 ◽

Vol 53 ◽

pp. 768-769

Author(s):

D.L. Spector ◽

S. Huang ◽

S. Kaurin

Keyword(s):

Rna Polymerase Ii ◽

Cell Nucleus ◽

Functional Organization ◽

Mrna Splicing ◽

Splicing Factors ◽

Interchromatin Granule Clusters ◽

Interchromatin Granule ◽

Nuclear Regions ◽

Relationship Of ◽

Perichromatin Fibrils

We have been interested in the organization of RNA polymerase II transcription and pre-mRNA splicing within the cell nucleus. Several models have been proposed for the functional organization of RNA within the eukaryotic nucleus and for the relationship of this organization to the distribution of pre-mRNA splicing factors. One model suggests that RNAs which must be spliced are capable of recruiting splicing factors to the sites of transcription from storage and/or reassembly sites. When one examines the organization of splicing factors in the nucleus in comparison to the sites of chromatin it is clear that splicing factors are not localized in coincidence with heterochromatin (Fig. 1). Instead, they are distributed in a speckled pattern which is composed of both perichromatin fibrils and interchromatin granule clusters. The perichromatin fibrils are distributed on the periphery of heterochromatin and on the periphery of interchromatin granule clusters as well as being diffusely distributed throughout the nucleoplasm. These nuclear regions have been previously shown to represent initial sites of incorporation of 3H-uridine.

Download Full-text

Mg++ - and Ca++-Induced Platelet Aggregation and ADP

Thrombosis and Haemostasis ◽

10.1055/s-0038-1654252 ◽

1970 ◽

Vol 24 (03/04) ◽

pp. 432-437 ◽

Cited By ~ 5

Author(s):

S Cronberg ◽

J. P Caen

Keyword(s):

Platelet Aggregation ◽

Pyruvate Kinase ◽

Pyruvic Acid ◽

Active Principle ◽

Platelet Suspension ◽

Edta Plasma ◽

Phosphoenol Pyruvic Acid

SummaryReports on platelet aggregation after addition of calcium or magnesium to EDTA- PRP or platelet suspensions were confirmed. An aggregating principle was found in the EDTA-plasma and the supernatant of the platelet suspensions. Aggregation by magnesium in a platelet suspension was inhibited by adenosine and phosphoenol- pyruvic acid and pyruvate kinase, which suggested that the active principle was identical with ADP. Degradation of ADP in EDTA plasma was blocked.It thus appears that aggregation induced by calcium or magnesium in EDTA-PRP and platelet suspension was due to accumulation of spontaneously liberated ADP, which was not degraded.

Download Full-text

Pyruvate kinase M2-deficiency in T cells leads to exacerbation of ConA hepatitis and alterations of T cell polarization

10.1055/s-0039-3402269 ◽

2020 ◽

Author(s):

K Moll ◽

S Weidemann ◽

S Huber ◽

G Tiegs ◽

AK Horst

Keyword(s):

T Cells ◽

T Cell ◽

Pyruvate Kinase ◽

Cell Polarization ◽

Pyruvate Kinase M2 ◽

T Cell Polarization

Download Full-text

Correlation between Faecal Tumour M2 Pyruvate Kinase and Colonoscopy for the Detection of Adenomatous Neoplasia in a Secondary Care Cohort

Journal of Gastrointestinal and Liver Diseases ◽

10.15403/jgld.2014.1121.251.m2p ◽

2016 ◽

Vol 25 (1) ◽

pp. 71-77 ◽

Cited By ~ 3

Author(s):

Ashley D. Bond ◽

Michael D. Burkitt ◽

David Sawbridge ◽

Bernard M. Corfe ◽

Chris S. Probert

Keyword(s):

Colorectal Cancer ◽

Cancer Screening ◽

Pyruvate Kinase ◽

Predictive Value ◽

Screening Programme ◽

Occult Blood ◽

Faecal Occult ◽

Faecal Samples ◽

Cancer Screening Programme ◽

Bowel Cancer Screening

Background & Aims: Colorectal cancer screening programmes that target detection and excision of adenomatous colonic polyps have been shown to reduce colorectal cancer related mortality. Many screening programmes include an initial faecal occult blood test (FOBt) prior to colonoscopy. To refine the selection of patients for colonoscopy other faecal-based diagnostic tools have been proposed, including tumour M2-pyruvate kinase (tM2-PK). To determine whether tM2-PK quantification may have a role in diverse settings we have assessed the assay in a cohort of patients derived from both the England bowel cancer screening programme (BCSP) and symptomatic individuals presenting to secondary care. Method. Patients undergoing colonoscopy provided faecal samples prior to bowel preparation. Faecal tM2-PK concentrations were measured by ELISA. Sensitivity, specificity, positive predictive value, negative predictive value and ROC analyses were calculated. Results. Ninety-six patients returned faecal samples: 50 of these with adenomas and 7 with cancer. Median age was 68. Median faecal tM2-PK concentration was 3.8 U/mL for individuals without neoplastic findings at colonoscopy, 7.7 U/mL in those with adenomas and 24.4 U/mL in subjects with colorectal cancer (both, p=0.01). ROC analysis demonstrated an AUROC of 0.66 (sensitivity 72.4%, specificity 48.7%, positive predictive value 67.7%, negative predictive value 36.7%). Amongst BCSP patients with a prior positive FOBt faecal tM2-PK was more abundant (median 6.4 U/mL, p=0.03) and its diagnostic accuracy was greater (AUROC 0.82). Conclusion. Our findings confirm that faecal tM2-PK ELISA may have utility as an adjunct to FOBt in a screening context, but do not support its use in symptomatic patients. Abbreviations: BCSP: Bowel cancer screening programme; EMR: Endoscopic mucosal resection; FAP: Familial adenomatous polyposis; FOBt: Faecal occult blood testing; NHS: National Health Service; tM2-PK: tumour M2-pyruvate kinase.

Download Full-text