Light-activated PTEN-dependent viral latency (1)

By: James V. Kohl | Published on: December 25, 2019

See: Dependence of RNA synthesis in isolated thymus nuclei on glycolysis, oxidative carbohydrate catabolism and a type of “oxidative phosphorylation” (1964)

The synthesis of RNA in isolated thymus nuclei is ATP dependent.

The energy required for biophysically constrained oxidative phosphorylation, viral latency, and cell type differentiation comes from food.
Amusing anecdote (for polymaths):
See: PTEN in Chromatin Remodeling 9/30/19 by Yang, J. and Yin, Y.

…we summarize the current understanding of roles of PTEN in controlling chromatin dynamics and global gene expression…

Y. Yin & J. Yang (2019) linked A Quick HYL1-Dependent Reactivation of MicroRNA Production Is Required for a Proper Developmental Response after Extended Periods of Light Deprivation from the light-activated Creation of microRNAs in plants to the ATP-dependent creation of RNA to  Yin Yang I as an Epimodulator of miRNAs in the Metastatic Cascade, which links microRNA biogenesis to biophysically constrained viral latency and the genesis of all biodiversity via the physiology of reproduction in all living genera.
Remember, the current understanding of roles for PTEN must include what is known about how Spindle-shaped viruses infect marine ammonia-oxidizing thaumarchaea 7/18/19, because:

…viral predation has a profound impact on thaumarchaeal functioning and mortality, thereby regulating global biogeochemical cycles.

More than 55 years after McEwen et al, established the facts about the ATP-dependent creation of RNA, it’s time to move forward. In 2014, I tried, but my invited review of nutritional epigenetics (food energy-dependent microRNA-mediated biophysically constrained viral latency) was returned without review.
See:  Nutrient-dependent pheromone-controlled ecological adaptations: from atoms to ecosystems 4/11/14 (preprint)
See for comparison:  PTENα, a PTEN isoform translated through alternative initiation, regulates mitochondrial function and energy metabolism 4/24/14

Our studies demonstrate the importance of eIF2A-mediated alternative translation for generation of protein diversity in eukaryotic systems and provide insights into the mechanism by which the PTEN family is involved in multiple cellular processes.

The claim that a PTEN isoform regulates energy-dependent mitochondrial function and energy metabolism eliminates the fact that the light-activated assembly of the microRNA-RNA-peptide nanocomplex must be linked from the ATP-dependent creation of RNA to the physiology of reproduction; to biophysically constrained viral latency; and to healthy longevity across all kingdoms.
Thank God, my invited review of nutritional epigenetics, which was returned by the guest editors of the journal “Nutrients” was published as Nutrient-dependent Pheromone-Controlled Ecological Adaptations: From Angstroms to Ecosystems 4/18/18
Attempts by others have continued to portray the ecological adaptations in the context of evolved and/or automagically maintained normal mitochondrial activity.
See for instance:PTENα regulates mitophagy and maintains mitochondrial quality control 8/1/18 (with my emphasis)

Damaged mitochondria produce excessive reactive oxygen species, causing DNA damage, lipid and protein oxidation, and ultimately cell death. A series of well-coordinated quality control processes have thus evolved to maintain normal mitochondrial activity.

 For comparison, all serious scientists know that the Creation of energy as information regulates mitophagy and the Creation of sunlight is required for mitochondrial quality control via microRNA-mediated autophagy. Why hasn’t that fact always been perfectly clear?
Thank God, the past obfuscation by Cold Spring Harbor Perspectives in Medicine, which should have ended  in 1999 with publication of Darwin’s Radio, ended with publication of The Complex Landscape of PTEN mRNA Regulation 12/23/19 by Sellars, E.Gabra, M.Salmena, L. (with my emphasis)

Phosphatase and tensin homolog deleted on chromosome 10 (PTEN) is a key tumor suppressor in the development and progression of different tumor types. Emerging data indicate that small reductions in PTEN protein levels can promote cancer. PTEN protein levels are tightly controlled by a plethora of mechanisms beginning with epigenetic and transcriptional regulation and ending with control of protein synthesis and stability. PTEN messenger RNA (mRNA) is also subject to exquisite regulation by microRNAs, coding and long noncoding RNAs, and RNA-binding proteins. Additionally, PTEN mRNA is markedly influenced by alternative splicing and variable polyadenylation. Herein we provide a synoptic description of the current understanding of the complex regulatory landscape of PTEN mRNA regulation including several specific processes that modulate its stability and expression, in the context of PTEN loss-associated cancers.

The US patent for the energy-dependent microRNA-mediated effective treatment and/or prevention of all cancers was issued on 12/25/18.
See: Methods and compositions for identifying a peptide having an intermolecular interaction with a target of interest

A system of a recombinant bacteriophage library and a target of interest complex, wherein the recombinant bacteriophage peptide library includes a plurality of peptides expressed on the surface of recombinant bacteriophages wherein each recombinant bacteriophage includes (a) a pill protein; wherein each pill protein includes (b) a peptide or polypeptide involved in an intermolecular interaction, which differs by at least one amino acid from other peptides or polypeptides in the library; and (c) a modified protease cleavage site proximal to the peptide, wherein the modified protease cleavage site is the same in each bacteriophage, the modified cleavage site having a reduced binding affinity to a protease, as compared to a non-modified cleavage site, and wherein the target of interest complex includes a protease, a flexible linker attached to the protease, and a target of interest attached to the flexible linker, wherein the target of interest participates in an intermolecular interaction.

See also: Proof of concept
Did I mention that the “…light-activated assembly of the microRNA-RNA-peptide nanocomplex must be linked from the physiology of reproduction to biophysically constrained viral latency and healthy longevity across all kingdoms…” via global biogeochemical cycles of energy-dependent protein biosynthesis and degradation?

See also:

  1. Connecting Genotype with Behavioral Phenotype in Mouse Models of Autism Associated with PTEN Mutations
    Clipperton-Allen, A. E.Page, D. T.
  2. PTEN: Bridging Endocytosis and Signaling
    Lee, M. F.Trotman, L. C.
  3. Precise Immunodetection of PTEN Protein in Human Neoplasia
    Pulido, R.Mingo, J.Gaafar, A.Nunes-Xavier, C. E.Luna, S.Torices, L.Angulo, J. C.Lopez, J. I.
  4. The Role of PTEN in Innate and Adaptive Immunity
    Taylor, H.Laurence, A. D. J.Uhlig, H. H.
  5. PTEN Nuclear Functions
    Ho, J.Cruise, E. S.Dowling, R. J. O.Stambolic, V.
  6. PTEN in Regulating Hematopoiesis and Leukemogenesis
    Wu, Y.Zhu, H.Wu, H.
  7. The Impact of Genetic Variants on PTEN Molecular Functions and Cellular Phenotypes
    Hasle, N.Matreyek, K. A.Fowler, D. M.
  8. PTEN in Autism and Neurodevelopmental Disorders
    Rademacher, S.Eickholt, B. J.
  9. Structural Mechanisms of PTEN Regulation
    Masson, G. R.Williams, R. L.
  10. Toward Systems Pathology for PTEN Diagnostics
    Haddadi, N.Travis, G.Nassif, N. T.Simpson, A. M.Marsh, D. J.
  11. PTEN in the Stroma
    Thies, K. A.Lefler, J. E.Leone, G.Ostrowski, M. C.
  12. Autism Spectrum Disorder Associated with Germline Heterozygous PTEN Mutations
    Frazier, T. W.
  13. PTEN in Hereditary and Sporadic Cancer
    Ngeow, J.Eng, C.
  14. PTEN Mouse Models of Cancer Initiation and Progression
    Lee, Y.-R.Pandolfi, P. P.
  15. Dual-Specific Protein and Lipid Phosphatase PTEN and Its Biological Functions
    Tu, T.Chen, J.Chen, L.Stiles, B. L.

After you realize how important the energy-dependent Creation of PTEN is to biophysically constrained viral latency, see Feynman’s comments on where the energy comes from:


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