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 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 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

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 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.

168 Post-radiation exit from G2 is related to endogenous RAF-1 protein levels in human cells expressing wild-type p53

1996 ◽  
Vol 36 (1) ◽  
pp. 242
Author(s):  
Hilmar Warenius ◽  
Tracy Gorman ◽  
Matthew Jones ◽  
Mark Jones ◽  
Christopher Thompson ◽  
...  
Keyword(s):  
Human Cells ◽  
Wild Type ◽  
Protein Levels ◽  
Post Radiation ◽  
Wild Type P53

scholarly journals Tunable protein synthesis by transcript isoforms in human cells

2015 ◽  
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 mRNA 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.

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