タンパク質分解、タンパク分解、蛋白分解、蛋白質分解、プロテオリシス

関: protein degradation、proteolyses、proteolytic、proteolytic degradation、proteolyze

WordNet

the hydrolysis of proteins into peptides and amino acids by cleavage of their peptide bonds
of or relating to proteolysis

Wikipedia preview

出典(authority):フリー百科事典『ウィキペディア（Wikipedia）』「2013/04/08 08:05:12」(JST)

wiki en

Proteolysis is the breakdown of proteins into smaller polypeptides or amino acids. This generally occurs by the hydrolysis of the peptide bond, and is most commonly achieved by cellular enzymes called proteases, but may also occur by intramolecular digestion, as well as by non-enzymatic methods such as the action of mineral acids and heat.

Proteolysis in organisms serves many purposes; for example, digestive enzymes break down proteins in food to provide amino acids for the organism, while proteolytic processing of polypeptide chain after its synthesis may be necessary for the production of an active protein. It is also important in the regulation of some physiological and cellular processes, as well as preventing the accumulation of unwanted or abnormal proteins in cells.

1 Post-translational proteolytic processing
- 1.1 Removal of N-terminal methionine
- 1.2 Removal of the signal sequence
- 1.3 Cleavage of polyprotein
- 1.4 Cleavage of precursor proteins
2 Protein degradation
- 2.1 Lysosome and proteasome
- 2.2 Rate of intracellular protein degradation
- 2.3 Digestion
3 Proteolysis in cellular regulation
- 3.1 Cell cycle regulation
- 3.2 Apoptosis
4 Regulatory domains in proteolysis
5 Proteolysis and diseases
6 Non-enzymatic proteolysis
7 Laboratory applications
8 Venoms
9 See also
10 References
11 External links

Post-translational proteolytic processing

Limited proteolysis of a polypeptide during or after translation in protein synthesis often occur for many proteins. This may involve removal of the N-terminal methionine, signal peptide, and/or the conversion of an inactive or non-functional protein to an active one. The precursor to the final functional form of protein is termed proprotein, and these proproteins may be first synthesized as preproprotein. For example, albumin is first synthesized as preproalbumin and contains an uncleaved signal peptide. This forms the proalbumin after the signal peptide is cleaved, and a further processing to remove the N-terminal 6-residue propeptide yields the mature form of the protein.^[1]

Removal of N-terminal methionine

The initiating methonine (and in prokaryotes, fMet) may be removed during translation of the nascent protein. For E. coli, fMet is efficiently removed if the second residue is small and uncharged, but not if the second residue is bulky and charged.^[2] In both prokaryotes and eukaryotes, the exposed N-terminal residue may determine the half-life of the protein according to the N-end rule.

Removal of the signal sequence

Proteins that are to be targeted to a particular organelle or for secretion have an N-terminal signal peptide that directs the protein to its final destination. This signal peptide is removed by proteolysis after their transport through a membrane.

Cleavage of polyprotein

Some proteins and most eukaryotic polypeptide hormones are synthesized as a large precursor polypeptide known as polyprotein that require proteolytic cleavage into individual smaller polypeptide chains. The polyprotein pro-opiomelanocortin (POMC) contains many polypeptide hormones. The cleavage pattern of POMC however may vary between different tissues, yielding different sets of polypeptide hormones from the same polyprotein.

Many viruses also produce their proteins initially as a single polypeptide chain that were translated from a polycistronic mRNA. This polypeptide is subsequently cleaved into individual polypeptide chains.^[1]

Cleavage of precursor proteins

Many proteins and hormones are synthesized in the form of their precursors - zymogens, proenzymes and prehormones. These proteins are cleaved to form their final active structures. Insulin, for example, is synthesized as preproinsulin which yields proinsulin after the signal peptide has been cleaved. To form the mature insulin, the proinsulin is then cleaved at two positions to yield two polypeptide chains linked by 2 disulphide bonds. Proinsulin is necessary for the folding of the polypeptide chain as the 2 polypeptide chains of insulin may not correctly assemble into the correct form while its precursor proinsulin do.

Proteases in particular are synthesized in the inactive form so that they may be safely stored in cells, and ready for released in sufficient quantity when required. This is to ensure that the protease is only activated in the correct location or context as inappropriate activation of these proteases can be very destructive for an organism. Proteolysis of the zymogen yields an active protein; for example, when trypsinogen is cleaved to form trypsin, a slight rearrangement of the protein structure occurs which completes the active site of the protease, thereby activating the protein.

Proteolysis can therefore be a method of regulating biological processes by turning inactive proteins into active ones. A good example is the blood clotting cascade whereby an initial event triggers a cascade of sequential proteolytic activation of many specific proteases, resulting in blood coagulation. The complement system of the immune response also involves a complex sequential proteolytic activation and interaction that result in an attack on invading pathogens.

Protein degradation

Proteolytic cleavage breaks down proteins in food extracellularly into smaller peptides and amino acids so that they may be absorbed and used by an organism. Proteins in cells are also constantly being broken down into amino acids. This intracellular degradation of protein serves a number of functions - it removes damaged and abnormal protein and prevent their accumulation, and it also serves to regulate cellular processes by removing enzymes and regulatory proteins that are no longer needed. The amino acids may then be reused for protein synthesis.

Structure of a proteasome. Its active sites are inside the tube (blue) where proteins are degraded.

Lysosome and proteasome

The intracellular degradation of protein may be achieved in two ways - proteolysis in lysosome, or a ubiquitin-dependent process which targets unwanted proteins to proteasome. The autophagy-lysosomal pathway is normally a non-selective process, but it may become selective upon starvation whereby proteins with peptide sequence KFERQ or similar are selectively broken down. The lysosome contains a large number of proteases such as cathepsins.

The ubiquitin-mediated process is selective. Proteins marked for degradation are covalently linked to ubiquitin. Many molecules of ubiquitin may be linked in tandem to a protein destined for degradation. The polyubiquinated protein is targeted to an ATP-dependent protease complex, the proteasome. The ubiquitin is released and reused, while the targeted protein is degraded.

Rate of intracellular protein degradation

Different proteins are degraded at different rate. Abnormal proteins are quickly degraded, while the rate of degradation of normal proteins may vary widely depending on their functions. Enzymes at important metabolic control points may be degraded much faster than those enzymes whose activity is largely constant under all physiological conditions. One of the most rapidly degraded protein is ornithine decarboxylase which has a half-life of 11 minutes. In contrast, other proteins like actin and myosin have half-life of a month or more, while haemoglobin essentially lasts for the entire life-time of erythrocyte.^[3]

The N-end rule may partially determine the half-life of a protein, and proteins with segments rich in proline, glutamine, serine, and threonine (the so-called PEST proteins) have short half-life.^[4] Other factors suspected to affect degradation rate include the rate deamination of glutamine and asparagine and oxidation of cystein, histidine and methionine, the absence of stabilizing ligands, the presence of attached carbohydrate or phosphate groups, the presence of free α-amino group, the negative charge of protein, and the flexibility and stability of the protein.^[3]

The rate of proteolysis may also depend on the physiological state of the cell, such as its hormonal state as well as nutritional status. In time of starvation, the rate of protein degradation increases.

Digestion

In human digestion, proteins in food are broken down into smaller peptide chains by digestive enzymes such as pepsin, trypsin, chymotrypsin, and elastase, and into amino acids by various enzymes such as carboxypeptidase, aminopeptidase and dipeptidase. It is necessary to break down proteins into small peptides (tripeptides and dipeptides) and amino acids so they can be absorbed by the intestines, and the absorbed tripeptides and dipeptides are also further broken into amino acids intracellularly before they enter the bloodstream.^[5] Different enzymes have different specificity for their substrate; trypsin for example cleaves the peptide bond after a positively charge residue (arginine and lysine), chymotrypsin cleaves the bond after an aromatic residue (phenylalanine, tyrosine, and tryptophan), elastase cleaves the bond after a small non-polar residue such as alanine or glycine.

In order to prevent inappropriate or premature activation of the digestive enzymes (they may, for example, trigger pancreatic self-digestion), these enzymes are secreted as inactive zymogen. The precursor of pepsin, pepsinogen, is secreted by the stomach, and is activated only in only in the acidic environment found in stomach. The pancreas secretes the precursors of a number of proteases, such trypsin and chymotrypsin. The zymogen of trypsin is trypsinogen which is activated by a very specific protease, enterokinase, which is secreted by the mucosa of the duodenum. The trypsin, once activated, can also cleave other trypsinogen as well as the precursors of other proteases such as chymotrypsin and carboxypeptidase.

In bacteria, a similar strategy of employing an inactive zymogen or prezymogen is used. Subtilisin which is produced by Bacillus subtilis is produced as preprosubtilisin, and is released only if the signal peptide is cleaved and autocatalytic proteolytic activation has occurred.

Proteolysis in cellular regulation

Proteolysis is also involved in the regulation of many cellular processes by activating or deactivating enzymes, transcription factors, and receptors, for example in the biosynthesis of cholesterol,^[6] or the mediation of thrombin signalling through protease-activated receptors.^[7]

Some enzymes at important metabolic control points such as ornithine decarboxylase is regulated entirely by its rate of synthesis and its rate of degradation. Other rapidly degraded proteins include the protein products of proto-oncogenes which play central roles in the regulation of cell growth.

Cell cycle regulation

Cyclins are a group of proteins that activate kinases involved in cell division. The degradation of cyclins is the key step that governs the exit from mitosis and progress into the next cell cycle.^[8] Cyclins accumulate in the course the cell cycle, then abruptly disappear just before the anaphase of mitosis. The cyclins are removed via a ubiquitin-mediated proteolytic pathway.

Apoptosis

Caspases are an important group of proteases involved in apoptosis. The precursors of caspase, procaspase, may be activated by proteolysis through its association with a protein complex that forms apoptosome, or by granzyme B, or via the death receptor pathways.

Regulatory domains in proteolysis

Protease may have one or more regulatory domains -

Calcium-binding domain - e.g. prothrombin, factor IX, X, VII, protein C in blood clotting cascade, calpain.
Kringle domain - e.g. in prothrombin it keeps the protease inactive.

Proteolysis and diseases

Abnormal proteolytic activity are associated with many diseases.^[9] In pancreatitis, leakage of proteases and their premature activation in the pancreas results in the self-digestion of the pancreas. People with diabetes mellitus may have increased lysosomal activity and the degradation of some proteins can increase significantly. Chronic inflammatory diseases such as rheumatoid arthritis may involve the release of lysosomal enzymes into extracellular space which break down surrounding tissues. Abnormal proteolysis and generation of peptides that aggregate in cells and their ineffective removal may result in many age-related neurological diseases such as Alzheimer.^[10]

Other diseases linked to aberrant proteolysis include muscular dystrophy, degenerative skin disorders, respiratory and gastrointestinal diseases, and malignancy.

Non-enzymatic proteolysis

Chemicals may be used in laboratory to target specific residue and cleave its peptide bond so that protein may be broken down into smaller polypeptides for analysis.^[11] Cyanogen bromide is often used to cleave the peptide bond after a methionine. Other methods may be used to specifically cleave tryptophanyl, aspartyl, cysteinyl, and asparaginyl peptide bonds. Acids such as trifluoroacetic acid and formic acid may also be used.

Strong mineral acids can readily hydrolyse the peptide bonds in a protein. However, some proteins are remarkably resistant to hydrolysis. One well-known example is ribonuclease A, and one method for its purification involves treatment of crude extracts with hot sulphuric acid so that other proteins become degraded while ribonuclease A is left intact.^[12]

Laboratory applications

Proteolysis is also used in research and diagnostic applications:

Cleavage of fusion protein so that the fusion partner and protein tag used in protein expression and purification may be removed. The proteases used have high degree of specificity, such as thrombin, enterokinase, and TEV protease, so that only the targeted sequence may be cleaved.
Complete inactivation of undesirable enzymatic activity or removal of unwanted proteins. For example, proteinase K, a broad spectrum proteinase stable in urea and SDS, is often used in the preparation of nucleic acids to remove unwanted nuclease contaminants which may otherwise degrade the DNA or RNA.^[13]
Partial inactivation, or changing the functionality, of specific protein. For example, treatment of DNA polymerase I with subtilisin yields the Klenow fragment which retains its polymerase function but lacks 5'-exonuclease activity.^[14]
In-gel digestion of proteins after separation by gel electrophoresis for the identification by mass spectrometry.
Digestion of proteins in solution for proteome analysis by liquid chromatography-mass spectrometry (LC-MS).
Analysis of the stability of folded domain under a wide range of conditions.^[15]
Increasing success rate of crystallisation projects ^[16]

Venoms

Certain types of venom, such as those produced by venomous snakes, can also cause proteolysis. These venoms are, in fact, complex digestive fluids that begin their work outside of the body. Proteolytic venoms cause a wide range of toxic effects,^[17] including effects that are:

cytotoxic (cell-destroying)
hemotoxic (blood-destroying)
myotoxic (muscle-destroying)
hemorrhagic (bleeding)

References

^ ^a ^b Thomas E Creighton (1993). Proteins: Structures and Molecular Properties (2nd ed.). W H Freeman and Company. pp. 78–86. ISBN 0-7167-2317-4.
^ P H Hirel, M J Schmitter, P Dessen, G Fayat, and S Blanquet (1989). "Extent of N-terminal methionine excision from Escherichia coli proteins is governed by the side-chain length of the penultimate amino acid". Proc Natl Acad Sci U S A 86 (21): 8247–51. doi:10.1073/pnas.86.21.8247. PMC 298257. PMID 2682640.
^ ^a ^b Thomas E Creighton (1993). "Chapter 10 - Degradation". Proteins: Structures and Molecular Properties (2nd ed.). W H Freeman and Company. pp. 463–473. ISBN 0-7167-2317-4.
^ Voet & Voet (1995). Biochemisty (2nd ed.). John Wiley & Sons. pp. 1010–1014. ISBN 0-471-58651-X.
^ Silk DB (1974). "Progress report. Peptide absorption in man". Gut 15 (6): 494–501. doi:10.1136/gut.15.6.494. PMC 1413009. PMID 4604970.
^ Michael S. Brown and Joseph L. Goldstein (May 1997). "The SREBP Pathway: Regulation of Cholesterol Metabolism by Proteolysis of a Membrane-Bound Transcription Factor". Cell 89 (3): 331–340. doi:10.1016/S0092-8674(00)80213-5. PMID 9150132.
^ Shaun R. Coughlin (2000). "Thrombin signalling and protease-activated receptors". Nature 407 (6801): 258–264. doi:10.1038/35025229. PMID 11001069.
^ Glotzer M, Murray AW, Kirschner MW (1991). "Cyclin is degraded by the ubiquitin pathway". Nature 349 (6305): 132–8. doi:10.1038/349132a0. PMID 1846030.
^ Kathleen M. Sakamoto (2002). "Ubiquitin-dependent proteolysis: its role in human diseases and the design of therapeutic strategies". Molecular Genetics and Metabolism 77 (1–2): 44–56. doi:10.1016/S1096-7192(02)00146-4. PMID 12359129.
^ De Strooper B. (2010). "Proteases and proteolysis in Alzheimer disease: a multifactorial view on the disease process". Physiological Reviews 90 (2): 465–94. doi:10.1152/physrev.00023.2009. PMID 20393191
^ Bryan John Smith (2002). "Chapter 71-75". In John M. Walker. The Protein Protocols Handbook (2 ed.). Humana Press. pp. 485–510. doi:10.1385/1592591698. ISBN 978-0-89603-940-7.
^ "Ribonuclease A". Protein Data Bank.
^ Hilz H, Wiegers U, Adamietz P (1975). "Stimulation of Proteinase K action by denaturing agents: application to the isolation of nucleic acids and the degradation of 'masked' proteins". European Journal of Biochemistry 56 (1): 103–108. doi:10.1111/j.1432-1033.1975.tb02211.x. PMID 1236799.
^ Klenow H and Henningsen I (1970). "Selective Elimination of the Exonuclease Activity of the Deoxyribonucleic Acid Polymerase from Escherichia coli B by Limited Proteolysis". Proc. Natl. Acad. Sci. USA 65 (1): 168–175. doi:10.1073/pnas.65.1.168. PMC 286206. PMID 4905667.
^ Minde DP; Maurice, Madelon M.; Rüdiger, Stefan G. D. (2012). "Determining biophysical protein stability in lysates by a fast proteolysis assay, FASTpp". In Uversky, Vladimir N. PLoS ONE 7 (10): e46147. doi:10.1371/journal.pone.0046147. PMC 3463568. PMID 23056252.
^ Wernimont, A; Edwards, A (2009). "In situ proteolysis to generate crystals for structure determination: An update". In Song, Haiwei. PLoS ONE 4 (4): e5094. doi:10.1371/journal.pone.0005094. PMC 2661377. PMID 19352432.
^ Hayes WK. 2005. Research on Biological Roles and Variation of Snake Venoms. Loma Linda University.

External links

Proteolysis at eMedicine Dictionary
Proteolysis MAP from Center on Proteolytic Pathways

UpToDate Contents

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1. 癌における悪液質の病因、臨床的特徴および評価 pathogenesis clinical features and assessment of cancer cachexia
2. 腎細胞癌の疫学、病理、および病因 epidemiology pathology and pathogenesis of renal cell carcinoma
3. von Willebrand病の分類および病態生理 classification and pathophysiology of von willebrand disease
4. インスリン作用 insulin action
5. 続発性（AA）アミロイドーシスの病因 pathogenesis of secondary aa amyloidosis

English Journal

Degradation of LIM domain-binding protein three during processing of Spanish dry-cured ham.

Gallego M, Mora L, Fraser PD, Aristoy MC, Toldrá F.Author information Instituto de Agroquímica y Tecnología de Alimentos (CSIC), Avenue Agustín Escardino 7, 46980 Paterna, Valencia, Spain.AbstractExtensive proteolysis takes place during the processing of dry-cured ham due to the action of muscle peptidases. The aim of this work was to study the degradation of LIM domain binding protein 3 (LDB3), which is located at the Z-lines of the sarcomere, at different times during the Spanish dry-cured ham processing (2, 3.5, 5, 6.5, and 9months). A total of 107 peptides have been identified by mass spectrometry, most of them generated from the first region of the protein sequence (position 1-90) providing evidence for the complexity and variability of proteolytic reactions throughout the whole process of dry-curing. Methionine oxidation has been observed in several peptides by the end of the process. The potential of some of the identified peptides to be used as biomarkers of dry-cured ham processing has also been considered.
Food chemistry.Food Chem.2014 Apr 15;149:121-8. doi: 10.1016/j.foodchem.2013.10.076. Epub 2013 Oct 25.
Extensive proteolysis takes place during the processing of dry-cured ham due to the action of muscle peptidases. The aim of this work was to study the degradation of LIM domain binding protein 3 (LDB3), which is located at the Z-lines of the sarcomere, at different times during the Spanish dry-cured
PMID 24295685

Cleavage of the calpain inhibitor, calpastatin, during postmortem ageing of beef skeletal muscle.

Huang F, Huang M, Zhang H, Guo B, Zhang D, Zhou G.Author information Institute of Agro-Products Processing Science and Technology, Chinese Academy of Agricultural Science, Beijing 100193, China.AbstractThe objective of this study was to investigate the contribution of caspase and calpain, on the proteolysis of calpastatin in postmortem beef muscle, by examining the influences of calpain inhibitor MDL-28170 and caspase-3 inhibitor DEVD-CHO on calpastatin degradation and the in vitro proteolysis of calpastatin by caspase-3, -6 and μ-calpain. In this study, both calpain- and caspase-3-inhibitors suppressed postmortem degradation of calpastatin. In vitro treatment of calpastatin with μ-calpain resulted in degradation products similar in size to those occurring naturally in aged beef muscle. With addition of caspase-3, only the 100kDa degradation fragment was present during the early phase of ageing, and subsequently, was likely to have been inactivated by calpain or other factors. Therefore, calpain was the major contributor to the proteolysis of calpastatin in postmortem beef muscle. While caspase-3 was involved in calpastatin degradation during the early postmortem period, calpastatin maybe plays an important role in bridging the gap between caspase and calpain systems.
Food chemistry.Food Chem.2014 Apr 1;148:1-6. doi: 10.1016/j.foodchem.2013.10.016. Epub 2013 Oct 10.
The objective of this study was to investigate the contribution of caspase and calpain, on the proteolysis of calpastatin in postmortem beef muscle, by examining the influences of calpain inhibitor MDL-28170 and caspase-3 inhibitor DEVD-CHO on calpastatin degradation and the in vitro proteolysis of
PMID 24262518

Validation of a new in vitro dynamic system to simulate infant digestion.

Ménard O, Cattenoz T, Guillemin H, Souchon I, Deglaire A, Dupont D, Picque D.Author information INRA, UMR 1253 Science et Technologie du Lait et de l'œuf, 35000 Rennes, France; AGROCAMPUS OUEST, UMR 1253 Science et Technologie du Lait et de l'œuf, 35000 Rennes, France.AbstractUnderstanding the mechanisms of infant formula disintegration in the infant gastrointestinal tract is a key step for developing new formulas with health benefits for the neonate. For ethical reasons, the access to in vivo data obtained on infants is limited. The use of animal models can be an alternative but these experiments are labour intensive, expensive and results obtained show high inter-individual variability, making their interpretation difficult. The aim of this work was to develop a simple in vitro dynamic gastrointestinal digestion system, for studying infant formula digestion, and to validate it by comparing the kinetics of proteolysis obtained in vitro with in vivo data collected from piglets. Results showed a good correlation between in vitro and in vivo data and confirmed the rapid hydrolysis of caseins in gastric conditions, whereas whey proteins appeared more resistant to digestion.
Food chemistry.Food Chem.2014 Feb 15;145:1039-45. doi: 10.1016/j.foodchem.2013.09.036. Epub 2013 Sep 14.
Understanding the mechanisms of infant formula disintegration in the infant gastrointestinal tract is a key step for developing new formulas with health benefits for the neonate. For ethical reasons, the access to in vivo data obtained on infants is limited. The use of animal models can be an altern
PMID 24128581

Proteolytic characterisation in grass carp sausage inoculated with Lactobacillus plantarum and Pediococcus pentosaceus.

Nie X, Lin S, Zhang Q.Author information College of Biological and Environmental Engineering, Zhejiang University of Technology, Hangzhou, Zhejiang 310014, China. Electronic address: niexiaohua2000@126.com.AbstractThe proteolysis in grass carp sausages inoculated with Lactobacillus plantarum ZY40 and Pediococcus pentosaceus GY23 was investigated. As fermentation progressed, sarcoplasmic and myofibrillar proteins in both sausages were obviously degraded, and the proteolytic process was more intense in sausages inoculated with P. pentosaceus GY23. The increases in α-amino nitrogen, trichloroacetic acid (TCA)-soluble peptides and free amino acids were also detected in both sausages. The differences in α-amino nitrogen content and free amino acids concentration were due to the activity of inoculated lactic acid bacteria, while endogenous enzymes contributed to the release of TCA-soluble peptides. Our findings indicate that lactic acid bacteria influence proteolytic characterisation in fermented fish sausage, with strain-dependent activity.
Food chemistry.Food Chem.2014 Feb 15;145:840-4. doi: 10.1016/j.foodchem.2013.08.096. Epub 2013 Sep 5.
The proteolysis in grass carp sausages inoculated with Lactobacillus plantarum ZY40 and Pediococcus pentosaceus GY23 was investigated. As fermentation progressed, sarcoplasmic and myofibrillar proteins in both sausages were obviously degraded, and the proteolytic process was more intense in sausages
PMID 24128554

Japanese Journal

Senescence-inducing stress promotes proteolysis of phosphoglycerate mutase via ubiquitin ligase Mdm2.

Mikawa Takumi,Maruyama Takeshi,Okamoto Koji,Nakagama Hitoshi,Lleonart Matilde E,Tsusaka Takeshi,Hori Kousuke,Murakami Itsuo,Izumi Taisuke,Takaori-Kondo Akifumi,Yokode Masayuki,Peters Gordon,Beach David,Kondoh Hiroshi
The Journal of cell biology 204(5), 729-745, 2014-03-03
細胞老化から癌化への変換のカギとなる解糖系制御機構解明に成功 -代謝を標的とした新しい抗がん剤開発に期待-. 京都大学プレスリリース. 2014-02-24.Despite the well-documented clinical significance of the Warburg effect, it remains unclear how the aggressive glycolyti …
NAID 120005385888

タンパク質膜内配列切断の制御と機能

富田泰輔
生化学 86(1), 28-40, 2014-02
NAID 40020011055

Degeneration of amyloid-ß fibrils caused by exposure to low-temperature atmospheric-pressure plasma in aqueous solution

Takai Eisuke,Ohashi Gai,Yoshida Tomonori,Sörgjerd Karin Margareta,Zako Tamotsu,Maeda Mizuo,Kitano Katsuhisa,Shiraki Kentaro,白木賢太郎
Applied physics letters 104(2), 023701, 2014-01
… These results suggested that an LF plasma jet could be utilized for the treatment of AD to eliminate neuritic plaque by accelerating the proteolysis of Aß fibrils. …
NAID 120005396076

Genipin Inhibits RANKL-Induced Osteoclast Differentiation Through Proteasome-Mediated Degradation of c-Fos Protein and Suppression of NF-κB Activation

Hoon Lee Chang,Kwak Sung-Chul,Kim Ju-Young,Mee Oh Hyun,Chual Rho Mun,Yoon Kwon-Ha,Yoo Wan-Hee,Su Lee Myeung,Oh Jaemin
Journal of Pharmacological Sciences 124(3), 344-353, 2014
… Taken together, our findings indicate that genipin down-regulated RANKL-induced osteoclast differentiation through inhibition of c-Fos protein proteolysis as well as inhibition of IκB degradation. …
NAID 130003391489

Related Pictures

★リンクテーブル★

リンク元	「好中球」「タンパク質分解」「タンパク分解」「proteolytic」「proteolyses」
拡張検索	「ubiquitin-mediated proteolysis」「ubiquitin-dependent proteolysis」「limited proteolysis」「regulated intramembrane proteolysis」

「好中球」

　　[★]

英: neutrophil (Z),neutrophile ,neutrophils
関: 血液、血球、白血球

特徴

マクロファージより貪食能が高い
非特異的感染防御に関与
寿命：1週間。(他の資料：1週間以内。血中で6-7時間,活性化時1-2日。)
好中球比率(対白血球)：50-60%。文献によっては50-70%
ケモカインによって走化能を示し、異物を貪食する

貪食→食胞形成→proteolysis (lysosome: 約30種類)

多数の特殊顆粒。少数のアズール顆粒。

分化・成熟

造血幹細胞→骨髄系前駆細胞(CFU-GEMM)→顆粒球,単球・マクロファージ系前駆細胞(CFU-GM)→骨髄芽球→好中球性前骨髄球→好中性骨髄球→好中性後骨髄球→杆状核好中球→分節核好中球

骨髄芽球：顆粒なし
　　↓
前骨髄球：アズール顆粒出現
　　↓
骨髄球：好中球に特異な顆粒（ALP、リゾチーム）が出現
　　↓
後骨髄球：核が分葉。細胞分裂（－）
　　↓
桿状核球：末梢血中に現れる�　　↓
　　↓
分葉核球：成熟細胞

顆粒

アズール顆粒。リソソームの一種

ヒドラーゼ、ミエロペルオキシダーゼ、リゾチーム、殺菌性膜透過促進蛋白、カテプシンG、エラスターゼ、コラゲナーゼ

特殊顆粒 (HIS.194)

IV型コラゲナーゼ、ホスホリパーゼA2、ラクトフェリン、リゾチーム、ファゴサイチン、アルカリホスファターゼ

成長とリンパ球・好中球数

PED.703

リンパ球数は生後1ヶ月以降に増加して6ヶ月～1年でピークとなり、以降減少して成人と同程度となる。
これに対して好中球は生下時にピークとなり、以降減少して成人と同程度となる。
生後一ヶ月までは好中球優位であり、1ヶ月～2-6歳まではリンパ球優位となり、以降好中球優位となる。

臨床関連

好中球減少症

末梢血好中球数1500/μl以下、特に500/μl以下 (定義：[1])

好中球増加症好中球増多症

末梢血好中球数7500/μ以上

慢性肉芽腫症：NADPH酸化酵素の異常による好中球の活性酸素産生障害をきたす疾患。常染色体劣性遺伝。
チェディアック・東症候群：細胞内輸送蛋白(CHS1)の調節の異常により巨大顆粒の形成、殺菌性蛋白・溶菌性酵素の食胞内放出が障害され、また好中球の遊走能が低下する疾患。常染色体劣性遺伝。

杆状核白血球と分節核好中球がある。

「タンパク質分解」

　　[★]

英: proteolysis、protein degradation、proteolytic degradation、proteolyses、proteolytic
関: タンパク分解、タンパク分解性、プロテオリシス、蛋白質分解、蛋白分解

-proteolysis

「タンパク分解」

　　[★]

英: proteolysis、proteolyses、protein degradation、proteolyze、proteolytic
関: タンパク質分解、タンパク分解性、プロテオリシス、蛋白質分解、蛋白分解

「proteolytic」

　　[★]

タンパク分解性の、タンパク分解の、タンパク質分解の

関: protein degradation、proteolyses、proteolysis、proteolytic degradation、proteolytically、proteolyze

「proteolyses」

　　[★]

タンパク質分解、タンパク分解、蛋白分解、蛋白質分解

関: protein degradation、proteolysis、proteolytic、proteolytic degradation、proteolyze

「ubiquitin-mediated proteolysis」

　　[★]

ユビキチン依存性タンパク質分解

関: ubiquitin-dependent proteolysis

「ubiquitin-dependent proteolysis」

　　[★]

ユビキチン依存性タンパク質分解

関: ubiquitin-mediated proteolysis

「limited proteolysis」

　　[★]

タンパク質限定加水分解、限定加水分解、限定分解

「regulated intramembrane proteolysis」

　　[★]

制御的膜内切断、制限的膜内切断

関: RIP

[creighton-1] Thomas E Creighton (1993). Proteins: Structures and Molecular Properties (2nd ed.). W H Freeman and Company. pp. 78–86. ISBN 0-7167-2317-4.

[2] P H Hirel, M J Schmitter, P Dessen, G Fayat, and S Blanquet (1989). "Extent of N-terminal methionine excision from Escherichia coli proteins is governed by the side-chain length of the penultimate amino acid". Proc Natl Acad Sci U S A 86 (21): 8247–51. doi:10.1073/pnas.86.21.8247. PMC 298257. PMID 2682640.

[degradation-3] Thomas E Creighton (1993). "Chapter 10 - Degradation". Proteins: Structures and Molecular Properties (2nd ed.). W H Freeman and Company. pp. 463–473. ISBN 0-7167-2317-4.

[4] Voet & Voet (1995). Biochemisty (2nd ed.). John Wiley & Sons. pp. 1010–1014. ISBN 0-471-58651-X.

[5] Silk DB (1974). "Progress report. Peptide absorption in man". Gut 15 (6): 494–501. doi:10.1136/gut.15.6.494. PMC 1413009. PMID 4604970.

[6] Michael S. Brown and Joseph L. Goldstein (May 1997). "The SREBP Pathway: Regulation of Cholesterol Metabolism by Proteolysis of a Membrane-Bound Transcription Factor". Cell 89 (3): 331–340. doi:10.1016/S0092-8674(00)80213-5. PMID 9150132.

[7] Shaun R. Coughlin (2000). "Thrombin signalling and protease-activated receptors". Nature 407 (6801): 258–264. doi:10.1038/35025229. PMID 11001069.

[8] Glotzer M, Murray AW, Kirschner MW (1991). "Cyclin is degraded by the ubiquitin pathway". Nature 349 (6305): 132–8. doi:10.1038/349132a0. PMID 1846030.

[9] Kathleen M. Sakamoto (2002). "Ubiquitin-dependent proteolysis: its role in human diseases and the design of therapeutic strategies". Molecular Genetics and Metabolism 77 (1–2): 44–56. doi:10.1016/S1096-7192(02)00146-4. PMID 12359129.

[10] De Strooper B. (2010). "Proteases and proteolysis in Alzheimer disease: a multifactorial view on the disease process". Physiological Reviews 90 (2): 465–94. doi:10.1152/physrev.00023.2009. PMID 20393191

[11] Bryan John Smith (2002). "Chapter 71-75". In John M. Walker. The Protein Protocols Handbook (2 ed.). Humana Press. pp. 485–510. doi:10.1385/1592591698. ISBN 978-0-89603-940-7.

[12] "Ribonuclease A". Protein Data Bank.

[13] Hilz H, Wiegers U, Adamietz P (1975). "Stimulation of Proteinase K action by denaturing agents: application to the isolation of nucleic acids and the degradation of 'masked' proteins". European Journal of Biochemistry 56 (1): 103–108. doi:10.1111/j.1432-1033.1975.tb02211.x. PMID 1236799.

[14] Klenow H and Henningsen I (1970). "Selective Elimination of the Exonuclease Activity of the Deoxyribonucleic Acid Polymerase from Escherichia coli B by Limited Proteolysis". Proc. Natl. Acad. Sci. USA 65 (1): 168–175. doi:10.1073/pnas.65.1.168. PMC 286206. PMID 4905667.

[15] Minde DP; Maurice, Madelon M.; Rüdiger, Stefan G. D. (2012). "Determining biophysical protein stability in lysates by a fast proteolysis assay, FASTpp". In Uversky, Vladimir N. PLoS ONE 7 (10): e46147. doi:10.1371/journal.pone.0046147. PMC 3463568. PMID 23056252.

[16] Wernimont, A; Edwards, A (2009). "In situ proteolysis to generate crystals for structure determination: An update". In Song, Haiwei. PLoS ONE 4 (4): e5094. doi:10.1371/journal.pone.0005094. PMC 2661377. PMID 19352432.

[-17] Hayes WK. 2005. Research on Biological Roles and Variation of Snake Venoms. Loma Linda University.

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proteolysis