Journal ArticleDOI
The Ubiquitin-Proteasome Proteolytic Pathway: Destruction for the Sake of Construction
TLDR
It is clear now that degradation of cellular proteins is a highly complex, temporally controlled, and tightly regulated process that plays major roles in a variety of basic pathways during cell life and death as well as in health and disease.Abstract:
Between the 1960s and 1980s, most life scientists focused their attention on studies of nucleic acids and the translation of the coded information. Protein degradation was a neglected area, conside...read more
Citations
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Cell Survival Responses to Environmental Stresses Via the Keap1-Nrf2-ARE Pathway
TL;DR: The development of Nrf2 knockout mice has provided key insights into the toxicological importance of this pathway, and this review highlights the key elements in this adaptive response to protection against acute and chronic cell injury provoked by environmental stresses.
Journal ArticleDOI
Robbins and Cotran pathologic basis of disease
TL;DR: The pathologic basis of disease is determined by X-ray diffraction analysis of the granuloma with an Higgs–Cotran–Bouchut–Seiden ratio of 3:1.
Journal ArticleDOI
Quality control in the endoplasmic reticulum
Lars Ellgaard,Ari Helenius +1 more
TL;DR: Recent progress is discussed in understanding the conformation-specific sorting of proteins at the level of ER retention and export, which is important for the fidelity of cellular functions.
Journal ArticleDOI
Protein degradation and protection against misfolded or damaged proteins
TL;DR: A full understanding of the pathogenesis of the protein-folding diseases will require greater knowledge of how misfolded proteins are recognized and selectively degraded.
Journal ArticleDOI
Comparing protein abundance and mRNA expression levels on a genomic scale
Dov Greenbaum,Christopher M. Colangelo,Christopher M. Colangelo,Kenneth R. Williams,Kenneth R. Williams,Mark Gerstein +5 more
TL;DR: This work merges many of the available yeast protein-abundance datasets, using the resulting larger 'meta-dataset' to find correlations between protein and mRNA expression, both globally and within smaller categories.
References
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Journal ArticleDOI
The Ubiquitin System
Avram Hershko,Aaron Ciechanover +1 more
TL;DR: This review discusses recent information on functions and mechanisms of the ubiquitin system and focuses on what the authors know, and would like to know, about the mode of action of ubi...
Journal ArticleDOI
CDK inhibitors: positive and negative regulators of G1-phase progression
TL;DR: This work challenges previous assumptions about how the G1/S transition of the mammalian cell cycle is governed, helps explain some enigmatic features of cell cycle control that also involve the functions of the retinoblastoma protein (Rb) and the INK4 proteins, and changes the thinking about how either p16 loss or overexpression of cyclin D-dependent kinases contribute to cancer.
Journal ArticleDOI
Targeting of HIF-alpha to the von Hippel-Lindau Ubiquitylation Complex by O2-Regulated Prolyl Hydroxylation
Panu Jaakkola,David R. Mole,Ya-Min Tian,Michael I. Wilson,Janine Gielbert,Simon J. Gaskell,Alex von Kriegsheim,Holger F. Hebestreit,Mridul Mukherji,Christopher J. Schofield,Patrick H. Maxwell,Christopher W. Pugh,Peter J. Ratcliffe +12 more
TL;DR: It is shown that the interaction between human pVHL and a specific domain of the HIF-1α subunit is regulated through hydroxylation of a proline residue by an enzyme the authors have termed Hif-α prolyl-hydroxylase (HIF-PH).
Journal ArticleDOI
Mutations in the parkin gene cause autosomal recessive juvenile parkinsonism
Tohru Kitada,Shuichi Asakawa,Nobutaka Hattori,Hiroto Matsumine,Yasuhiro Yamamura,Shinsei Minoshima,Masayuki Yokochi,Yoshikuni Mizuno,Nobuyoshi Shimizu +8 more
TL;DR: Mutations in the newly identified gene appear to be responsible for the pathogenesis of Autosomal recessive juvenile parkinsonism, and the protein product is named ‘Parkin’.
Journal ArticleDOI
The tumour suppressor protein VHL targets hypoxia-inducible factors for oxygen-dependent proteolysis
Patrick H. Maxwell,Michael S. Wiesener,Gin-Wen Chang,Steven C. Clifford,Emma C. Vaux,Matthew Edward Cockman,Charles C. Wykoff,Christopher W. Pugh,Eamonn R. Maher,Peter J. Ratcliffe,Peter J. Ratcliffe +10 more
TL;DR: It is indicated that the interaction between HIF-1 and pVHL is iron dependent, and that it is necessary for the oxygen-dependent degradation of HIF α-subunits, which may underlie the angiogenic phenotype of VHL-associated tumours.