- 関
- hyperphosphorylated
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出典(authority):フリー百科事典『ウィキペディア(Wikipedia)』「2016/08/09 18:58:31」(JST)
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Hyperphosphorylation occurs when a biochemical with multiple phosphorylation sites is fully saturated. Hyperphosphorylation is one of the signalling mechanisms used by the cell to regulate mitosis. When these mechanisms fail, developmental problems or cancer are a likely outcome. The mechanism appears to be largely conserved throughout eukaryote species.
The dynamics of mitosis are similar to a state machine. In a healthy cell, checkpoints between phases, permit a new phase to begin only when the previous phase is complete and successful. At these checkpoints, gatekeeper molecules block or allow events, depending on their level of phosphorylation. Kinases are responsible for adding phosphate groups and phosphatases for removing them. Cyclins are molecules that manage the timing of cell cycle events. Cyclin dependent kinases pair up with cyclins to become operational. Cyclins are named because they are created or destroyed at predetermined points within the cell cycle. Kinase inhibitors add another level of modulation. Kinase inhibitors are grouped into classes and are assigned not very descriptive acronyms. These include INKS for inhibitors of kinase, KIPS for kinase inhibitors and CKIPS for cyclin dependent kinases inhibitors.
Scientists have used a variety of tools to unravel the role of hyperphosphorylation. These include the study of knockout genes, the use of antibodies to block receptors on particular molecules, the use of temperature sensitive mutants, and microarrays to monitor the expression of particular genes. Yeast are a popular species for study because of the rapid cell cycle.
Rb is one of the most studied checkpoint molecules. It is so named because defects in Rb are linked to retinoblastoma. In its unphosphorylated state it blocks the transition from G0 or resting state to S or synthesis. It does this in at least 3 ways. It inhibits RNA synthesis, it prevents chromosomes from unwinding and it binds E2F, a factor needed for DNA synthesis. When it is hyperphosphorylated, Rb becomes inactive, releasing bound E2F and allowing phase S to proceed.
Wee is a protein that operates at the G2 to metaphase checkpoint. Wee becomes active if errors occur in the DNA synthesis phase. It blocks entry into metaphase until the problem is resolved. Like Rb, wee becomes inactive when hyperphosphorylated.
In contrast Mad1 is active when hyperphosphorylated. In its active state it is part of the checkpoint that blocks transition to anaphase. Cdc2, part of the metaphase entry checkpoint, is active depending on the pattern of phosphorylation.
Protein primary structure and posttranslational modifications
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General |
- Peptide bond
- Protein biosynthesis
- Proteolysis
- Racemization
- N-O acyl shift
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N terminus |
- Acetylation
- Carbamylation
- Formylation
- Glycation
- Methylation
- Myristoylation (Gly)
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C terminus |
- Amidation
- Glycosyl phosphatidylinositol (GPI)
- O-methylation
- Detyrosination
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Single specific AAs |
Serine/Threonine
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- Phosphorylation
- Dephosphorylation
- Glycosylation
- Methylidene-imidazolone (MIO) formation
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Tyrosine
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- Phosphorylation
- Dephosphorylation
- Sulfation
- Porphyrin ring linkage
- Adenylylation
- Flavin linkage
- Topaquinone (TPQ) formation
- Detyrosination
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Cysteine
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- Palmitoylation
- Prenylation
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Aspartate
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Glutamate
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- Carboxylation
- Methylation
- Polyglutamylation
- Polyglycylation
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Asparagine
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- Deamidation
- Glycosylation
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Glutamine
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Lysine
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- Methylation
- Acetylation
- Acylation
- Adenylylation
- Hydroxylation
- Ubiquitination
- Sumoylation
- ADP-ribosylation
- Deamination
- Oxidative deamination to aldehyde
- O-glycosylation
- Imine formation
- Glycation
- Carbamylation
- Succinylation
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Arginine
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- Citrullination
- Methylation
- ADP-ribosylation
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Proline
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Histidine
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- Diphthamide formation
- Adenylylation
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Tryptophan
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Crosslinks between two AAs |
Cysteine-Cysteine
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Methionine-Hydroxylysine
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Lysine-Tyrosylquinone
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- Lysine tyrosylquinone (LTQ) formation
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Tryptophan-Tryptophylquinone
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- Tryptophan tryptophylquinone (TTQ) formation
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Three consecutive AAs
(chromophore formation) |
Serine–Tyrosine–Glycine
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- p-Hydroxybenzylidene-imidazolinone formation
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Histidine–Tyrosine–Glycine
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- 4-(p-hydroxybenzylidene)-5-imidazolinone formation
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Crosslinks between four AAs |
Allysine-Allysine-Allysine-Lysine
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UpToDate Contents
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English Journal
- Morin reverses neuropathological and cognitive impairments in APPswe/PS1dE9 mice by targeting multiple pathogenic mechanisms.
- Du Y1, Qu J2, Zhang W2, Bai M1, Zhou Q1, Zhang Z2, Li Z3, Miao J4.
- Neuropharmacology.Neuropharmacology.2016 Sep;108:1-13. doi: 10.1016/j.neuropharm.2016.04.008. Epub 2016 Apr 8.
- Alzheimer's disease (AD) is the most common form of dementia worldwide, characterized by progressive cognitive impairment and multiple distinct neuropathological features. Currently, there are no available therapies to delay or block the disease progression. Thus, the disease-modifying therapies are
- PMID 27067919
- Endoplasmic reticulum stress mediates JNK-dependent IRS-1 serine phosphorylation and results in Tau hyperphosphorylation in amyloid β oligomer-treated PC12 cells and primary neurons.
- Zhang X1, Tang S1, Zhang Q1, Shao W1, Han X1, Wang Y1, Du Y2.
- Gene.Gene.2016 Aug 10;587(2):183-93. doi: 10.1016/j.gene.2016.05.018. Epub 2016 May 13.
- AIMS: Endoplasmic reticulum stress (ERS) and insulin signaling impairment are commonly observed in Alzheimer's disease (AD), but the association between these two factors in AD has not been carefully studied. In peripheral insulin signaling impairment, ERS interferes with insulin signaling through c
- PMID 27185631
- Leucine induced dephosphorylation of Sestrin2 promotes mTORC1 activation.
- Kimball SR1, Gordon BS2, Moyer JE2, Dennis MD2, Jefferson LS2.
- Cellular signalling.Cell Signal.2016 Aug;28(8):896-906. doi: 10.1016/j.cellsig.2016.03.008. Epub 2016 Mar 21.
- The studies described herein were designed to explore the role of Sestrin2 in mediating the selective action of leucine to activate mTORC1. The results demonstrate that Sestrin2 is a phosphoprotein and that its phosphorylation state is responsive to the availability of leucine, but not other essenti
- PMID 27010498
Japanese Journal
- アルツハイマー病の固有病変(神経原線[維]塊と老人斑)の発現範囲 : 38歳で発症し25年の経過をとった家族性アルツハイマー病例の病理・解剖学的研究
- 吉村 教
- 弘前医療福祉大学紀要 2(1), 1-14, 2011-03-30
- … On theother hand, it is believed that by GSK3β which is activated by the overproduction of Aβ insideneurons, hyperphosphorylation of tau proceeds and soluble oligomers of tau polymerize to be insolublegranular aggregates, and then become larger insoluble NFT. …
- NAID 40019065546
- SAMP8大脳に発現するアルツハイマー病関連タンパク質において検出されたD-アミノ酸量の増加
- 河西 亜希子
- 日本女性科学者の会学術誌 11(1), 57-64, 2010
- これまで、生物を構成するアミノ酸はL-体が主体であると考えられてきた。しかし近年、L-アミノ酸の光学異性体であるD-アミノ酸の生体内での機能が明らかになりつつある。本研究では、加齢とともに発症リスクの高まるアルツハイマー病に注目し、アルツハイマー病関連タンパク質に含有されるD-アミノ酸の加齢に伴う量の変化を解析した。実験にはアルツハイマー病のモデル動物である老化促進モデル動物SAMP8系統(SAM …
- NAID 130001077731
Related Links
- hyperphosphorylation (plural hyperphosphorylations) (biochemistry) The state of being fully phosphorylated, so that all potential phosphorylation sites are occupied Related terms [edit] hyperphosphorylate hypophosphorylation [edit] ...
- How does hyper-phosphorylated tau cause nerve cell degeneration? How does hyper-phosphorylated tau cause nerve cell degeneration? Tweet Lead investigator: Dr Amritpal Mudher Institution: University of Southampton ...
★リンクテーブル★
[★]
- 英
- hyperphosphorylation、hyperphosphorylated
- 関
- リン酸化過剰、高リン酸化、高リン酸化型
[★]
- 関
- hyperphosphorylation
[★]
- 英
- hyperphosphorylation
- 関
- 過剰リン酸化