scholarly journals Complex mutual regulation of facilitates chromatin transcription (FACT) subunits on both mRNA and protein levels in human cells

Cell Cycle ◽  
2013 ◽  
Vol 12 (15) ◽  
pp. 2423-2434 ◽  
Author(s):  
Alfiya Safina ◽  
Henry Garcia ◽  
Mairead Commane ◽  
Olga Guryanova ◽  
Seamus Degan ◽  
...  
Keyword(s):  
Human Cells ◽  
Protein Levels ◽  
Mutual Regulation ◽  
Facilitates Chromatin Transcription

scholarly journals Topoisomerase II is regulated by translationally controlled tumor protein for cell survival during organ growth in Drosophila

2021 ◽  
Vol 12 (9) ◽  
Author(s):  
Dae-Wook Yang ◽  
Jung-Wan Mok ◽  
Stephanie B. Telerman ◽  
Robert Amson ◽  
Adam Telerman ◽  
...  
Keyword(s):  
Cell Survival ◽  
Topoisomerase Ii ◽  
Wing Disc ◽  
Organ Development ◽  
Translationally Controlled Tumor Protein ◽  
Protein Levels ◽  
Eye Disc ◽  
Mutual Regulation

AbstractRegulation of cell survival is critical for organ development. Translationally controlled tumor protein (TCTP) is a conserved protein family implicated in the control of cell survival during normal development and tumorigenesis. Previously, we have identified a human Topoisomerase II (TOP2) as a TCTP partner, but its role in vivo has been unknown. To determine the significance of this interaction, we examined their roles in developing Drosophila organs. Top2 RNAi in the wing disc leads to tissue reduction and caspase activation, indicating the essential role of Top2 for cell survival. Top2 RNAi in the eye disc also causes loss of eye and head tissues. Tctp RNAi enhances the phenotypes of Top2 RNAi. The depletion of Tctp reduces Top2 levels in the wing disc and vice versa. Wing size is reduced by Top2 overexpression, implying that proper regulation of Top2 level is important for normal organ development. The wing phenotype of Tctp RNAi is partially suppressed by Top2 overexpression. This study suggests that mutual regulation of Tctp and Top2 protein levels is critical for cell survival during organ development.

scholarly journals Tunable protein synthesis by transcript isoforms in human cells

eLife ◽  
2016 ◽  
Vol 5 ◽  
Author(s):  
Stephen N Floor ◽  
Jennifer A Doudna
Keyword(s):  
Translational Control ◽  
Protein Production ◽  
Dynamic Range ◽  
Human Cells ◽  
Untranslated Regions ◽  
Specific Expression ◽  
Transcript Isoforms ◽  
Protein Levels ◽  
Eukaryotic Genes ◽  
Control Protein

Eukaryotic genes generate multiple RNA transcript isoforms though alternative transcription, splicing, and polyadenylation. However, the relationship between human transcript diversity and protein production is complex as each isoform can be translated differently. We fractionated a polysome profile and reconstructed transcript isoforms from each fraction, which we term Transcript Isoforms in Polysomes sequencing (TrIP-seq). Analysis of these data revealed regulatory features that control ribosome occupancy and translational output of each transcript isoform. We extracted a panel of 5′ and 3′ untranslated regions that control protein production from an unrelated gene in cells over a 100-fold range. Select 5′ untranslated regions exert robust translational control between cell lines, while 3′ untranslated regions can confer cell type-specific expression. These results expose the large dynamic range of transcript-isoform-specific translational control, identify isoform-specific sequences that control protein output in human cells, and demonstrate that transcript isoform diversity must be considered when relating RNA and protein levels.

scholarly journals Effect of PKC/NF-κB on the Regulation of P2X3 Receptor in Dorsal Root Ganglion in Rats with Sciatic Nerve Injury

2020 ◽  
Vol 2020 ◽  
pp. 1-8
Author(s):  
Xue Li ◽  
Jie Yuan ◽  
Xuan Yu ◽  
Qin Zhang ◽  
Bangyong Qin
Keyword(s):  
Neuropathic Pain ◽  
Dorsal Root ◽  
Regulatory Mechanism ◽  
Intrathecal Injection ◽  
Intrathecal Administration ◽  
Pyrrolidine Dithiocarbamate ◽  
Withdrawal Threshold ◽  
Protein Levels ◽  
Kinase C ◽  
Mutual Regulation

Background. Protein kinase C (PKC), nuclear factor-kappa B p65 (NF-κB p65), and P2X3 receptor (P2X3R) play significant roles in the sensitization and transduction of nociceptive signals, which are considered as potential targets for the treatment of neuropathic pain. However, the mechanisms and relationships among them have not been clearly clarified. Methods. 80 rats were randomized and divided into 10 groups (n = 8). Sciatic chronic constriction injury (CCI) rats were intrathecally administered with bisindolylmaleimide I (GF109203X), a PKC-selective antagonist once a day, or pyrrolidine dithiocarbamate (PDTC), an NF-κB inhibitor twice a day. Sham-operated rats were intrathecally administered with saline. Thermal withdrawal latency (TWL) and mechanical withdrawal threshold (MWT) were evaluated in all the groups before CCI operation (baseline) and on the 1st, 3rd, 7th, 10th, and 14th day after CCI operation. Protein levels of p-PKCα, p-NF-κB p65, and P2X3R were analyzed in the CCI ipsilateral L4–6 dorsal root ganglions (DRGs). Results. Intrathecal injection of GF109203X or PDTC alleviated the TWL and MWT in the following 2 weeks after CCI surgery. The protein levels of p-PKCα, p-NF-κB p65, and P2X3R in the ipsilateral DRGs significantly increased after CCI operation, which could be partly reversed by intrathecal administration of GF109203X or PDTC. Conclusion. The upregulation of p-PKCα, p-NF-κB p65, and P2X3R expression in the DRGs of CCI rats was involved in the occurrence and development of neuropathic pain. Phosphorylated PKCα and phosphorylated NF-κB p65 regulated with each other. Phosphorylated NF-κB p65 and PKCα have a mutual regulation relationship with P2X3R, respectively, while the specific regulatory mechanism needs further research.

scholarly journals Gene‐specific correlation of RNA and protein levels in human cells and tissues

2016 ◽  
Vol 12 (10) ◽  
pp. 883 ◽  
Author(s):  
Fredrik Edfors ◽  
Frida Danielsson ◽  
Björn M Hallström ◽  
Lukas Käll ◽  
Emma Lundberg ◽  
...  
Keyword(s):  
Human Cells ◽  
Protein Levels

Variability and memory of protein levels in human cells

Nature ◽  
2006 ◽  
Vol 444 (7119) ◽  
pp. 643-646 ◽  
Author(s):  
Alex Sigal ◽  
Ron Milo ◽  
Ariel Cohen ◽  
Naama Geva-Zatorsky ◽  
Yael Klein ◽  
...  
Keyword(s):  
Human Cells ◽  
Protein Levels

scholarly journals DNMT1 deficiency triggers mismatch repair defects in human cells through depletion of repair protein levels in a process involving the DNA damage response

2011 ◽  
Vol 20 (16) ◽  
pp. 3241-3255 ◽  
Author(s):  
Jayne E.P. Loughery ◽  
Philip D. Dunne ◽  
Karla M. O'Neill ◽  
Richard R. Meehan ◽  
Jennifer R. McDaid ◽  
...  
Keyword(s):  
Dna Damage ◽  
Mismatch Repair ◽  
Dna Damage Response ◽  
Human Cells ◽  
Protein Levels ◽  
Repair Protein ◽  
Damage Response

scholarly journals Protein quality control degron-containing substrates are differentially targeted in the cytoplasm and nucleus by ubiquitin ligases

Genetics ◽  
2020 ◽  
Vol 217 (1) ◽  
Author(s):  
Christopher M Hickey ◽  
Carolyn Breckel ◽  
Mengwen Zhang ◽  
William C Theune ◽  
Mark Hochstrasser
Keyword(s):  
Quality Control ◽  
Protein Quality ◽  
Protein Quality Control ◽  
Ubiquitin Ligases ◽  
Ubiquitin Proteasome System ◽  
Human Cells ◽  
Covalent Attachment ◽  
Protein Levels ◽  
Ubiquitin System ◽  
C Terminus

Abstract Intracellular proteolysis by the ubiquitin–proteasome system regulates numerous processes and contributes to protein quality control (PQC) in all eukaryotes. Covalent attachment of ubiquitin to other proteins is specified by the many ubiquitin ligases (E3s) expressed in cells. Here we determine the E3s in Saccharomyces cerevisiae that function in degradation of proteins bearing various PQC degradation signals (degrons). The E3 Ubr1 can function redundantly with several E3s, including nuclear-localized San1, endoplasmic reticulum/nuclear membrane-embedded Doa10, and chromatin-associated Slx5/Slx8. Notably, multiple degrons are targeted by more ubiquitylation pathways if directed to the nucleus. Degrons initially assigned as exclusive substrates of Doa10 were targeted by Doa10, San1, and Ubr1 when directed to the nucleus. By contrast, very short hydrophobic degrons—typical targets of San1—are shown here to be targeted by Ubr1 and/or San1, but not Doa10. Thus, distinct types of PQC substrates are differentially recognized by the ubiquitin system in a compartment-specific manner. In human cells, a representative short hydrophobic degron appended to the C-terminus of GFP-reduced protein levels compared with GFP alone, consistent with a recent study that found numerous natural hydrophobic C-termini of human proteins can act as degrons. We also report results of bioinformatic analyses of potential human C-terminal degrons, which reveal that most peptide substrates of Cullin-RING ligases (CRLs) are of low hydrophobicity, consistent with previous data showing CRLs target degrons with specific sequences. These studies expand our understanding of PQC in yeast and human cells, including the distinct but overlapping PQC E3 substrate specificity of the cytoplasm and nucleus.

Sign in / Sign up

Export Citation Format

Share Document