Abstract:
:Analysis of the human genome reveals that approximately a third of all open reading frames code for proteins that enter the endoplasmic reticulum (ER), demonstrating the importance of this organelle for global protein maturation. The path taken by a polypeptide through the secretory pathway starts with its translocation across or into the ER membrane. It then must fold and be modified correctly in the ER before being transported via the Golgi apparatus to the cell surface or another destination. Being physically segregated from the cytosol means that the ER lumen has a distinct folding environment. It contains much of the machinery for fulfilling the task of protein production, including complex pathways for folding, assembly, modification, quality control, and recycling. Importantly, the compartmentalization means that several modifications that do not occur in the cytosol, such as glycosylation and extensive disulfide bond formation, can occur to secreted proteins to enhance their stability before their exposure to the extracellular milieu. How these various machineries interact during the normal pathway of folding and protein secretion is the subject of this review.
journal_name
Annu Rev Biochemjournal_title
Annual review of biochemistryauthors
Braakman I,Bulleid NJdoi
10.1146/annurev-biochem-062209-093836subject
Has Abstractpub_date
2011-01-01 00:00:00pages
71-99eissn
0066-4154issn
1545-4509journal_volume
80pub_type
杂志文章,评审abstract::Clathrin-mediated endocytosis (CME) is the major endocytic pathway in mammalian cells. It is responsible for the uptake of transmembrane receptors and transporters, for remodeling plasma membrane composition in response to environmental changes, and for regulating cell surface signaling. CME occurs via the assembly an...
journal_title:Annual review of biochemistry
pub_type: 杂志文章,评审
doi:10.1146/annurev-biochem-062917-012644
更新日期:2018-06-20 00:00:00
abstract::The existence and function of actin in the nucleus has been hotly debated for forty years. Recently, beta-actin was found to be a component of mammalian SWI/SNF-like BAF chromatin remodeling complexes and still more recently other SWI/SNF-related chromatin remodeling complexes in yeast, flies, and man. Although the fu...
journal_title:Annual review of biochemistry
pub_type: 杂志文章,评审
doi:10.1146/annurev.biochem.71.110601.135507
更新日期:2002-01-01 00:00:00
abstract::Prenylation is a class of lipid modification involving covalent addition of either farnesyl (15-carbon) or geranylgeranyl (20-carbon) isoprenoids to conserved cysteine residues at or near the C-terminus of proteins. Known prenylated proteins include fungal mating factors, nuclear lamins, Ras and Ras-related GTP-bindin...
journal_title:Annual review of biochemistry
pub_type: 杂志文章,评审
doi:10.1146/annurev.bi.65.070196.001325
更新日期:1996-01-01 00:00:00
abstract::The field of vitamin D metabolism and mechanism of action has continued to be very active. Autoradiography has shown specific nuclear localization of 1,25-(OH)2D3 in target organs prior to initiation of mechanism of action. Specific nuclear localization has also been demonstrated in a variety of other tissues not prev...
journal_title:Annual review of biochemistry
pub_type: 杂志文章,评审
doi:10.1146/annurev.bi.52.070183.002211
更新日期:1983-01-01 00:00:00
abstract::Early influences led me first to medical school with a view to microbiology, but I felt the lack of a deeper foundation and changed to chemistry, which in turn led me to physics and mathematics. I moved to the University of Cape Town to work on the X-ray crystallography of some small organic compounds. I developed a n...
journal_title:Annual review of biochemistry
pub_type: 传,历史文章,杂志文章
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更新日期:2010-01-01 00:00:00
abstract::Ryanodine receptors (RyRs)/Ca2+ release channels, on the endoplasmic and sarcoplasmic reticulum of most cell types, are required for intracellular Ca2+ release involved in diverse cellular functions, including muscle contraction and neurotransmitter release. The large cytoplasmic domain of the RyR serves as a scaffold...
journal_title:Annual review of biochemistry
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journal_title:Annual review of biochemistry
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abstract::Active transport between the nucleus and cytoplasm involves primarily three classes of macromolecules: substrates, adaptors, and receptors. Some transport substrates bind directly to an import or an export receptor while others require one or more adaptors to mediate formation of a receptor-substrate complex. Once ass...
journal_title:Annual review of biochemistry
pub_type: 杂志文章,评审
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更新日期:1998-01-01 00:00:00
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journal_title:Annual review of biochemistry
pub_type: 杂志文章,评审
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更新日期:2002-01-01 00:00:00
abstract::Central to the classical hematopoietic stem cell (HSC) paradigm is the concept that the maintenance of blood cell numbers is exclusively executed by a discrete physical entity: the transplantable HSC. The HSC paradigm has served as a stereotypic template in stem cell biology, yet the search for rare, hardwired profess...
journal_title:Annual review of biochemistry
pub_type: 杂志文章,评审
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更新日期:2018-06-20 00:00:00
abstract::I was born in China and would have remained there but for the tumultuous events that led many of my generation to the United States for graduate studies. Norman Davidson introduced me to DNA when I became a postdoctoral fellow in his group at the California Institute of Technology in 1964, and a fortuitous conversatio...
journal_title:Annual review of biochemistry
pub_type: 传,历史文章,杂志文章
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更新日期:2009-01-01 00:00:00
abstract::Alterations of chromatin structure have been shown to be crucial for response to cell signaling and for programmed gene expression in development. Posttranslational histone modifications influence changes in chromatin structure both directly and by targeting or activating chromatin-remodeling complexes. Histone modifi...
journal_title:Annual review of biochemistry
pub_type: 杂志文章,评审
doi:10.1146/annurev-biochem-061809-175347
更新日期:2011-01-01 00:00:00
abstract::Magic angle spinning (MAS) NMR studies of amyloid and membrane proteins and large macromolecular complexes are an important new approach to structural biology. However, the applicability of these experiments, which are based on (13)C- and (15)N-detected spectra, would be enhanced if the sensitivity were improved. Here...
journal_title:Annual review of biochemistry
pub_type: 杂志文章,评审
doi:10.1146/annurev-biochem-060614-034206
更新日期:2015-01-01 00:00:00
abstract::Telomeres are essential for genome stability in all eukaryotes. Changes in telomere functions and the associated chromosomal abnormalities have been implicated in human aging and cancer. Telomeres are composed of repetitive sequences that can be maintained by telomerase, a complex containing a reverse transcriptase (h...
journal_title:Annual review of biochemistry
pub_type: 杂志文章,评审
doi:10.1146/annurev.biochem.73.071403.160049
更新日期:2004-01-01 00:00:00
abstract::Multistep chemical reactions are increasingly seen as important in a growing number of complex biotransformations. Covalently attached prosthetic groups or swinging arms, and their associated protein domains, are essential to the mechanisms of active-site coupling and substrate channeling in a number of the multifunct...
journal_title:Annual review of biochemistry
pub_type: 杂志文章,评审
doi:10.1146/annurev.biochem.69.1.961
更新日期:2000-01-01 00:00:00
abstract::Cys2His2 zinc finger proteins offer a stable and versatile framework for the design of proteins that recognize desired target sites on double-stranded DNA. Individual fingers from these proteins have a simple beta beta alpha structure that folds around a central zinc ion, and tandem sets of fingers can contact neighbo...
journal_title:Annual review of biochemistry
pub_type: 杂志文章,评审
doi:10.1146/annurev.biochem.70.1.313
更新日期:2001-01-01 00:00:00
abstract::Several lines of experimentation suggest that endogenous retinoids, metabolites of vitamin A, play a role in the anterior/posterior development of the central body axis and the limbs of vertebrates. High levels of endogenous retinoids have been detected in proximity to these developing axes in a variety of vertebrate ...
journal_title:Annual review of biochemistry
pub_type: 杂志文章,评审
doi:10.1146/annurev.bi.64.070195.001221
更新日期:1995-01-01 00:00:00
abstract::This review focuses on molecular mechanisms that underlie the communication between the nuclear and mitochondrial genomes in eukaryotic cells. These genomes interact in at least two ways. First, they contribute essential subunit polypeptides to important mitochondrial proteins; second, they collaborate in the synthesi...
journal_title:Annual review of biochemistry
pub_type: 杂志文章,评审
doi:10.1146/annurev.bi.65.070196.003023
更新日期:1996-01-01 00:00:00
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journal_title:Annual review of biochemistry
pub_type: 杂志文章,评审
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更新日期:2016-06-02 00:00:00
abstract::Endocytic mechanisms control the lipid and protein composition of the plasma membrane, thereby regulating how cells interact with their environments. Here, we review what is known about mammalian endocytic mechanisms, with focus on the cellular proteins that control these events. We discuss the well-studied clathrin-m...
journal_title:Annual review of biochemistry
pub_type: 杂志文章,评审
doi:10.1146/annurev.biochem.78.081307.110540
更新日期:2009-01-01 00:00:00
abstract::Death-associated protein kinase (DAPk) is the founding member of a newly classified family of Ser/Thr kinases, whose members not only possess significant homology in their catalytic domains, but also share cell death-associated functions. The realization that DAPk is a tumor suppressor gene, whose expression is lost i...
journal_title:Annual review of biochemistry
pub_type: 杂志文章,评审
doi:10.1146/annurev.biochem.75.103004.142615
更新日期:2006-01-01 00:00:00
abstract::The T lymphocytes of the vertebrate immune system look for changes that take place within the organism by examining a display of peptides at the cell surface. These peptides are presented by the products of the major histocompatibility complex (MHC). MHC class I products present peptides derived by proteolysis of cyto...
journal_title:Annual review of biochemistry
pub_type: 杂志文章,评审
doi:10.1146/annurev.bi.64.070195.002335
更新日期:1995-01-01 00:00:00
abstract::Glycoproteins have a wide distribution in nature and serve a vast number of functions. There are glycoprotein enzymes and hormones; glycoproteins are found in blood and secretions, in cell membranes, and in connective tissue. Of all the biologically occurring macromolecules the glycoproteins, which consist of carbohyd...
journal_title:Annual review of biochemistry
pub_type: 杂志文章,评审
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更新日期:1976-01-01 00:00:00
abstract::The RNA polymerase II transcription cycle is often divided into three major stages: initiation, elongation, and termination. Research over the last decade has blurred these divisions and emphasized the tightly regulated transitions that occur as RNA polymerase II synthesizes a transcript from start to finish. Transcri...
journal_title:Annual review of biochemistry
pub_type: 杂志文章,评审
doi:10.1146/annurev-biochem-060614-034457
更新日期:2015-01-01 00:00:00
abstract::Mechanisms of chemical reaction can often be predicted by determining the dependence of the lifetime of reaction intermediates on the structure of the reactants. When there is no lifetime in the presence of another reactant or catalyst the reaction proceeds through an enforced concerted mechanism. Noncovalent binding ...
journal_title:Annual review of biochemistry
pub_type: 传,历史文章,杂志文章
doi:10.1146/annurev.biochem.66.1.1
更新日期:1997-01-01 00:00:00
abstract::Regulation of gene transcription is vitally important for the maintenance of normal cellular homeostasis. Failure to correctly regulate gene expression, or to deal with problems that arise during the transcription process, can lead to cellular catastrophe and disease. One of the ways cells cope with the challenges of ...
journal_title:Annual review of biochemistry
pub_type: 杂志文章,评审
doi:10.1146/annurev-biochem-052110-120012
更新日期:2012-01-01 00:00:00
abstract::The determination of several structures of nuclear receptor ligand binding domains (LBD) has led to new insights into the mechanism of action of this very important class of receptors. This review describes and compares the different LBD structures and their relationship to the function of the nuclear receptors. The r...
journal_title:Annual review of biochemistry
pub_type: 杂志文章,评审
doi:10.1146/annurev.biochem.68.1.559
更新日期:1999-01-01 00:00:00
abstract::G protein-coupled receptor kinases (GRKs) constitute a family of six mammalian serine/threonine protein kinases that phosphorylate agonist-bound, or activated, G protein-coupled receptors (GPCRs) as their primary substrates. GRK-mediated receptor phosphorylation rapidly initiates profound impairment of receptor signal...
journal_title:Annual review of biochemistry
pub_type: 杂志文章,评审
doi:10.1146/annurev.biochem.67.1.653
更新日期:1998-01-01 00:00:00
abstract::The rhodopsin crystal structure provides a structural basis for understanding the function of this and other G protein-coupled receptors (GPCRs). The major structural motifs observed for rhodopsin are expected to carry over to other GPCRs, and the mechanism of transformation of the receptor from inactive to active for...
journal_title:Annual review of biochemistry
pub_type: 杂志文章,评审
doi:10.1146/annurev.biochem.75.103004.142743
更新日期:2006-01-01 00:00:00
abstract::This review is concerned with the structures and mechanisms of a superfamily of regulatory GTP hydrolases (G proteins). G proteins include Ras and its close homologs, translation elongation factors, and heterotrimeric G proteins. These proteins share a common structural core, exemplified by that of p21ras (Ras), and s...
journal_title:Annual review of biochemistry
pub_type: 杂志文章,评审
doi:10.1146/annurev.biochem.66.1.639
更新日期:1997-01-01 00:00:00