LIVIVO - Search results -

Search results

Result 1 - 10 of total 95

Search options

Article ; Online: Functions and regulation of the serine/threonine protein kinase CK1 family: moving beyond promiscuity.

Fulcher, Luke J / Sapkota, Gopal P

2020 Volume 477, Issue 23, Page(s) 4603–4621

Abstract: Regarded as constitutively active enzymes, known to participate in many, diverse biological processes, the intracellular regulation bestowed on the CK1 family of serine/threonine protein kinases is critically important, yet poorly understood. Here, we ... ...

Abstract	Regarded as constitutively active enzymes, known to participate in many, diverse biological processes, the intracellular regulation bestowed on the CK1 family of serine/threonine protein kinases is critically important, yet poorly understood. Here, we provide an overview of the known CK1-dependent cellular functions and review the emerging roles of CK1-regulating proteins in these processes. We go on to discuss the advances, limitations and pitfalls that CK1 researchers encounter when attempting to define relationships between CK1 isoforms and their substrates, and the challenges associated with ascertaining the correct physiological CK1 isoform for the substrate of interest. With increasing interest in CK1 isoforms as therapeutic targets, methods of selectively inhibiting CK1 isoform-specific processes is warranted, yet challenging to achieve given their participation in such a vast plethora of signalling pathways. Here, we discuss how one might shut down CK1-specific processes, without impacting other aspects of CK1 biology.
MeSH term(s)	Animals ; Casein Kinase I/genetics ; Casein Kinase I/metabolism ; Humans ; Isoenzymes/genetics ; Isoenzymes/metabolism ; Signal Transduction ; Substrate Specificity
Chemical Substances	Isoenzymes ; Casein Kinase I (EC 2.7.11.1)
Language	English
Publishing date	2020-06-30
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't ; Review
ZDB-ID	2969-5
ISSN	1470-8728 ; 0006-2936 ; 0306-3275 ; 0264-6021
ISSN (online)	1470-8728
ISSN	0006-2936 ; 0306-3275 ; 0264-6021
DOI	10.1042/BCJ20200506
Database	MEDical Literature Analysis and Retrieval System OnLINE

In stock of ZB MED Cologne/Königswinter

Uc I Zs.110: Show issues

Location:
Je nach Verfügbarkeit (siehe Angabe bei Bestand)
bis Jg. 2021: Bestellungen von Artikeln über das Online-Bestellformular
ab Jg. 2022: Lesesaal (EG)

Order via subito

This service is chargeable due to the Delivery terms set by subito. Orders including an article and supplementary material will be classified as separate orders. In these cases, fees will be demanded for each order.

Details ▾
- See ZB MED holdings
- Order with fees

Article ; Online: Mitotic kinase anchoring proteins: the navigators of cell division.

Fulcher, Luke J / Sapkota, Gopal P

Cell cycle (Georgetown, Tex.)

2020 Volume 19, Issue 5, Page(s) 505–524

Abstract: The coordinated activities of many protein kinases, acting on multiple protein substrates, ensures the error-free progression through mitosis of eukaryotic cells. Enormous research effort has thus been devoted to studying the roles and regulation of ... ...

Abstract	The coordinated activities of many protein kinases, acting on multiple protein substrates, ensures the error-free progression through mitosis of eukaryotic cells. Enormous research effort has thus been devoted to studying the roles and regulation of these mitotic kinases, and to the identification of their physiological substrates. Central for the timely deployment of specific protein kinases to their appropriate substrates during the cell division cycle are the many anchoring proteins, which serve critical regulatory roles. Through direct association, anchoring proteins are capable of modulating the catalytic activity and/or sub-cellular distribution of the mitotic kinases they associate with. The key roles of some anchoring proteins in cell division are well-established, whilst others are still being unearthed. Here, we review the current knowledge on anchoring proteins for some mitotic kinases, and highlight how targeting anchoring proteins for inhibition, instead of the mitotic kinases themselves, could be advantageous for disrupting the cell division cycle.
MeSH term(s)	Animals ; Aurora Kinases/metabolism ; Cyclin-Dependent Kinases/metabolism ; Cyclins/metabolism ; Humans ; M Phase Cell Cycle Checkpoints ; Microtubule-Associated Proteins/metabolism ; Mitosis/drug effects ; Protein Kinases/metabolism
Chemical Substances	Cyclins ; Knl1 protein, human ; Microtubule-Associated Proteins ; Protein Kinases (EC 2.7.-) ; Aurora Kinases (EC 2.7.11.1) ; Cyclin-Dependent Kinases (EC 2.7.11.22)
Language	English
Publishing date	2020-02-12
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't ; Review
ZDB-ID	2146183-1
ISSN	1551-4005 ; 1538-4101 ; 1554-8627
ISSN (online)	1551-4005
ISSN	1538-4101 ; 1554-8627
DOI	10.1080/15384101.2020.1728014
Database	MEDical Literature Analysis and Retrieval System OnLINE

In stock of ZB MED Cologne/Königswinter

Zs.A 5881: Show issues

Location:
Je nach Verfügbarkeit (siehe Angabe bei Bestand)
bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular
Jg. 1995 - 2021: Lesesall (2.OG)
ab Jg. 2022: Lesesaal (EG)

Order via subito

Details ▾
- See ZB MED holdings
- Order with fees

Article ; Online: An affinity-directed phosphatase, AdPhosphatase, system for targeted protein dephosphorylation.

Simpson, Luke M / Fulcher, Luke J / Sathe, Gajanan / Brewer, Abigail / Zhao, Jin-Feng / Squair, Daniel R / Crooks, Jennifer / Wightman, Melanie / Wood, Nicola T / Gourlay, Robert / Varghese, Joby / Soares, Renata F / Sapkota, Gopal P

Cell chemical biology

2023 Volume 30, Issue 2, Page(s) 188–202.e6

Abstract: Reversible protein phosphorylation, catalyzed by protein kinases and phosphatases, is a fundamental process that controls protein function and intracellular signaling. Failure of phospho-control accounts for many human diseases. While a kinase ... ...

Abstract	Reversible protein phosphorylation, catalyzed by protein kinases and phosphatases, is a fundamental process that controls protein function and intracellular signaling. Failure of phospho-control accounts for many human diseases. While a kinase phosphorylates multiple substrates, a substrate is often phosphorylated by multiple kinases. This renders phospho-control at the substrate level challenging, as it requires inhibition of multiple kinases, which would thus affect other kinase substrates. Here, we describe the development and application of the affinity-directed phosphatase (AdPhosphatase) system for targeted dephosphorylation of specific phospho-substrates. By deploying the Protein Phosphatase 1 or 2A catalytic subunits conjugated to an antigen-stabilized anti-GFP nanobody, we can promote the dephosphorylation of two independent phospho-proteins, FAM83D or ULK1, knocked in with GFP-tags using CRISPR-Cas9, with exquisite specificity. By redirecting protein phosphatases to neo-substrates through nanobody-mediated proximity, AdPhosphatase can alter the phospho-status and function of target proteins and thus, offers a new modality for potential drug discovery approaches.
MeSH term(s)	Humans ; Cell Cycle Proteins/metabolism ; Microtubule-Associated Proteins/metabolism ; Phosphorylation ; Protein Kinases/metabolism ; Protein Phosphatase 2/metabolism ; Substrate Specificity ; Phosphoric Monoester Hydrolases/metabolism
Chemical Substances	Cell Cycle Proteins ; FAM83D protein, human ; Microtubule-Associated Proteins ; Protein Kinases (EC 2.7.-) ; Protein Phosphatase 2 (EC 3.1.3.16) ; Phosphoric Monoester Hydrolases (EC 3.1.3.2)
Language	English
Publishing date	2023-01-30
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ISSN	2451-9448
ISSN (online)	2451-9448
DOI	10.1016/j.chembiol.2023.01.003
Database	MEDical Literature Analysis and Retrieval System OnLINE

Order via subito

Inter-library loan at ZB MED

Your chosen title can be delivered directly to ZB MED Cologne location if you are registered as a user at ZB MED Cologne.

Article ; Online: Advances in targeted degradation of endogenous proteins.

Röth, Sascha / Fulcher, Luke J / Sapkota, Gopal P

Cellular and molecular life sciences : CMLS

2019 Volume 76, Issue 14, Page(s) 2761–2777

Abstract: Protein silencing is often employed as a means to aid investigations in protein function and is increasingly desired as a therapeutic approach. Several types of protein silencing methodologies have been developed, including targeting the encoding genes, ... ...

Abstract	Protein silencing is often employed as a means to aid investigations in protein function and is increasingly desired as a therapeutic approach. Several types of protein silencing methodologies have been developed, including targeting the encoding genes, transcripts, the process of translation or the protein directly. Despite these advances, most silencing systems suffer from limitations. Silencing protein expression through genetic ablation, for example by CRISPR/Cas9 genome editing, is irreversible, time consuming and not always feasible. Similarly, RNA interference approaches warrant prolonged treatments, can lead to incomplete protein depletion and are often associated with off-target effects. Targeted proteolysis has the potential to overcome some of these limitations. The field of targeted proteolysis has witnessed the emergence of many methodologies aimed at targeting specific proteins for degradation in a spatio-temporal manner. In this review, we provide an appraisal of the different targeted proteolytic systems and discuss their applications in understanding protein function, as well as their potential in therapeutics.
MeSH term(s)	Gene Editing ; Humans ; Proteasome Endopeptidase Complex/genetics ; Proteasome Endopeptidase Complex/metabolism ; Proteins/genetics ; Proteins/metabolism ; Proteolysis ; Ubiquitination
Chemical Substances	Proteins ; Proteasome Endopeptidase Complex (EC 3.4.25.1)
Language	English
Publishing date	2019-04-27
Publishing country	Switzerland
Document type	Journal Article ; Review
ZDB-ID	1358415-7
ISSN	1420-9071 ; 1420-682X
ISSN (online)	1420-9071
ISSN	1420-682X
DOI	10.1007/s00018-019-03112-6
Database	MEDical Literature Analysis and Retrieval System OnLINE

Full text online

Accessible to users with ZB MED library card

In stock of ZB MED Cologne/Königswinter

Zs.A 195: Show issues

Location:
Je nach Verfügbarkeit (siehe Angabe bei Bestand)
bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular
Jg. 1995 - 2021: Lesesall (1.OG)
ab Jg. 2022: Lesesaal (EG)

Order via subito

Details ▾

Article ; Online: An Affinity-directed Protein Missile (AdPROM) System for Targeted Destruction of Endogenous Proteins.

Macartney, Thomas J / Sapkota, Gopal P / Fulcher, Luke J

Bio-protocol

2017 Volume 7, Issue 22, Page(s) e2614

Abstract: ... proteolysis of endogenous proteins of interest (POI) ( Fulcher ...

Abstract	We recently reported an Affinity-directed PROtein Missile (AdPROM) system for the targeted proteolysis of endogenous proteins of interest (POI) ( Fulcher
Language	English
Publishing date	2017-11-20
Publishing country	United States
Document type	Journal Article
ZDB-ID	2833269-6
ISSN	2331-8325 ; 2331-8325
ISSN (online)	2331-8325
ISSN	2331-8325
DOI	10.21769/BioProtoc.2614
Database	MEDical Literature Analysis and Retrieval System OnLINE

Order via subito

Article ; Online: PP6 regulation of Aurora A-TPX2 limits NDC80 phosphorylation and mitotic spindle size.

Sobajima, Tomoaki / Kowalczyk, Katarzyna M / Skylakakis, Stefanos / Hayward, Daniel / Fulcher, Luke J / Neary, Colette / Batley, Caleb / Kurlekar, Samvid / Roberts, Emile / Gruneberg, Ulrike / Barr, Francis A

The Journal of cell biology

2023 Volume 222, Issue 5

Abstract: Amplification of the mitotic kinase Aurora A or loss of its regulator protein phosphatase 6 (PP6) have emerged as drivers of genome instability. Cells lacking PPP6C, the catalytic subunit of PP6, have amplified Aurora A activity, and as we show here, ... ...

Abstract	Amplification of the mitotic kinase Aurora A or loss of its regulator protein phosphatase 6 (PP6) have emerged as drivers of genome instability. Cells lacking PPP6C, the catalytic subunit of PP6, have amplified Aurora A activity, and as we show here, enlarged mitotic spindles which fail to hold chromosomes tightly together in anaphase, causing defective nuclear structure. Using functional genomics to shed light on the processes underpinning these changes, we discover synthetic lethality between PPP6C and the kinetochore protein NDC80. We find that NDC80 is phosphorylated on multiple N-terminal sites during spindle formation by Aurora A-TPX2, exclusively at checkpoint-silenced, microtubule-attached kinetochores. NDC80 phosphorylation persists until spindle disassembly in telophase, is increased in PPP6C knockout cells, and is Aurora B-independent. An Aurora-phosphorylation-deficient NDC80-9A mutant reduces spindle size and suppresses defective nuclear structure in PPP6C knockout cells. In regulating NDC80 phosphorylation by Aurora A-TPX2, PP6 plays an important role in mitotic spindle formation and size control and thus the fidelity of cell division.
MeSH term(s)	Cell Cycle Proteins/metabolism ; Kinetochores/metabolism ; Microtubules/metabolism ; Mitosis ; Nuclear Proteins/metabolism ; Phosphoprotein Phosphatases/metabolism ; Phosphorylation ; Spindle Apparatus/metabolism ; Cytoskeletal Proteins/metabolism ; Aurora Kinase A/metabolism ; Microtubule-Associated Proteins/metabolism
Chemical Substances	Cell Cycle Proteins ; Nuclear Proteins ; Phosphoprotein Phosphatases (EC 3.1.3.16) ; protein phosphatase 6 (EC 3.1.3.16) ; Cytoskeletal Proteins ; Aurora Kinase A (EC 2.7.11.1) ; Microtubule-Associated Proteins
Language	English
Publishing date	2023-03-10
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	218154-x
ISSN	1540-8140 ; 0021-9525
ISSN (online)	1540-8140
ISSN	0021-9525
DOI	10.1083/jcb.202205117
Database	MEDical Literature Analysis and Retrieval System OnLINE

In stock of ZB MED Cologne/Königswinter

Ub I Zs.190: Show issues

Location:
Je nach Verfügbarkeit (siehe Angabe bei Bestand)
bis Jg. 2021: Bestellungen von Artikeln über das Online-Bestellformular
ab Jg. 2022: Lesesaal (EG)

Order via subito

Details ▾
- See ZB MED holdings
- Order with fees

Article: Advances in targeted degradation of endogenous proteins

Röth, Sascha / Fulcher, Luke J / Sapkota, Gopal P

Cellular and molecular life sciences. 2019 July, v. 76, no. 14

2019

Abstract	Protein silencing is often employed as a means to aid investigations in protein function and is increasingly desired as a therapeutic approach. Several types of protein silencing methodologies have been developed, including targeting the encoding genes, transcripts, the process of translation or the protein directly. Despite these advances, most silencing systems suffer from limitations. Silencing protein expression through genetic ablation, for example by CRISPR/Cas9 genome editing, is irreversible, time consuming and not always feasible. Similarly, RNA interference approaches warrant prolonged treatments, can lead to incomplete protein depletion and are often associated with off-target effects. Targeted proteolysis has the potential to overcome some of these limitations. The field of targeted proteolysis has witnessed the emergence of many methodologies aimed at targeting specific proteins for degradation in a spatio-temporal manner. In this review, we provide an appraisal of the different targeted proteolytic systems and discuss their applications in understanding protein function, as well as their potential in therapeutics.
Keywords	CRISPR-Cas systems ; RNA interference ; gene editing ; genes ; messenger RNA ; protein depletion ; protein synthesis ; proteins ; proteolysis ; therapeutics ; translation (genetics)
Language	English
Dates of publication	2019-07
Size	p. 2761-2777.
Publishing place	Springer International Publishing
Document type	Article
Note	Review
ZDB-ID	1358415-7
ISSN	1420-9071 ; 1420-682X
ISSN (online)	1420-9071
ISSN	1420-682X
DOI	10.1007/s00018-019-03112-6
Database	NAL-Catalogue (AGRICOLA)

In stock of ZB MED Bonn / Germany

Z 4' 47/14: Show issues

Order via subito

Inter-library loan at ZB MED

Your chosen title can be delivered directly to ZB MED Cologne location if you are registered as a user at ZB MED Cologne.

Details ▾
- See ZB MED holdings
- Order with fees

Article ; Online: Targeting endogenous proteins for degradation through the affinity-directed protein missile system.

Fulcher, Luke J / Hutchinson, Luke D / Macartney, Thomas J / Turnbull, Craig / Sapkota, Gopal P

Open biology

2017 Volume 7, Issue 5

Abstract: Targeted proteolysis of endogenous proteins is desirable as a research toolkit and in therapeutics. CRISPR/Cas9-mediated gene knockouts are irreversible and often not feasible for many genes. Similarly, RNA interference approaches necessitate prolonged ... ...

Abstract	Targeted proteolysis of endogenous proteins is desirable as a research toolkit and in therapeutics. CRISPR/Cas9-mediated gene knockouts are irreversible and often not feasible for many genes. Similarly, RNA interference approaches necessitate prolonged treatments, can lead to incomplete knockdowns and are often associated with off-target effects. Targeted proteolysis can overcome these limitations. In this report, we describe an affinity-directed protein missile (AdPROM) system that harbours the von Hippel-Lindau (VHL) protein, the substrate receptor of the Cullin2 (CUL2) E3 ligase complex, tethered to polypeptide binders that selectively bind and recruit endogenous target proteins to the CUL2-E3 ligase complex for ubiquitination and proteasomal degradation. By using synthetic monobodies that selectively bind the protein tyrosine phosphatase SHP2 and a camelid-derived VHH nanobody that selectively binds the human ASC protein, we demonstrate highly efficient AdPROM-mediated degradation of endogenous SHP2 and ASC in human cell lines. We show that AdPROM-mediated loss of SHP2 in cells impacts SHP2 biology. This study demonstrates for the first time that small polypeptide binders that selectively recognize endogenous target proteins can be exploited for AdPROM-mediated destruction of the target proteins.
MeSH term(s)	A549 Cells ; Blotting, Western ; CARD Signaling Adaptor Proteins/genetics ; CARD Signaling Adaptor Proteins/metabolism ; Cell Line, Tumor ; Cullin Proteins/genetics ; Cullin Proteins/metabolism ; Gene Knock-In Techniques/methods ; Humans ; Proteasome Endopeptidase Complex/metabolism ; Protein Tyrosine Phosphatase, Non-Receptor Type 11/genetics ; Protein Tyrosine Phosphatase, Non-Receptor Type 11/metabolism ; Proteolysis ; RNA Interference ; Tumor Suppressor Proteins/genetics ; Tumor Suppressor Proteins/metabolism ; Ubiquitination ; Von Hippel-Lindau Tumor Suppressor Protein/genetics ; Von Hippel-Lindau Tumor Suppressor Protein/metabolism
Chemical Substances	CARD Signaling Adaptor Proteins ; CUL2 protein, human ; Cullin Proteins ; PYCARD protein, human ; Tumor Suppressor Proteins ; Von Hippel-Lindau Tumor Suppressor Protein (EC 2.3.2.27) ; Protein Tyrosine Phosphatase, Non-Receptor Type 11 (EC 3.1.3.48) ; Proteasome Endopeptidase Complex (EC 3.4.25.1) ; VHL protein, human (EC 6.3.2.-)
Language	English
Publishing date	2017-05-08
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2630944-0
ISSN	2046-2441 ; 2046-2441
ISSN (online)	2046-2441
ISSN	2046-2441
DOI	10.1098/rsob.170066
Database	MEDical Literature Analysis and Retrieval System OnLINE

Order via subito

Article ; Online: Targeting endogenous proteins for degradation through the affinity-directed protein missile system

Luke J. Fulcher / Luke D. Hutchinson / Thomas J. Macartney / Craig Turnbull / Gopal P. Sapkota

Open Biology, Vol 7, Iss

2017 Volume 5

Abstract	Targeted proteolysis of endogenous proteins is desirable as a research toolkit and in therapeutics. CRISPR/Cas9-mediated gene knockouts are irreversible and often not feasible for many genes. Similarly, RNA interference approaches necessitate prolonged treatments, can lead to incomplete knockdowns and are often associated with off-target effects. Targeted proteolysis can overcome these limitations. In this report, we describe an affinity-directed protein missile (AdPROM) system that harbours the von Hippel–Lindau (VHL) protein, the substrate receptor of the Cullin2 (CUL2) E3 ligase complex, tethered to polypeptide binders that selectively bind and recruit endogenous target proteins to the CUL2-E3 ligase complex for ubiquitination and proteasomal degradation. By using synthetic monobodies that selectively bind the protein tyrosine phosphatase SHP2 and a camelid-derived VHH nanobody that selectively binds the human ASC protein, we demonstrate highly efficient AdPROM-mediated degradation of endogenous SHP2 and ASC in human cell lines. We show that AdPROM-mediated loss of SHP2 in cells impacts SHP2 biology. This study demonstrates for the first time that small polypeptide binders that selectively recognize endogenous target proteins can be exploited for AdPROM-mediated destruction of the target proteins.
Keywords	proteolysis ; adprom ; ubiquitination ; shp2 ; asc ; nanobody ; Biology (General) ; QH301-705.5
Subject code	612
Language	English
Publishing date	2017-01-01T00:00:00Z
Publisher	The Royal Society
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

Full text online

Full text

Inter-library loan at ZB MED

Your chosen title can be delivered directly to ZB MED Cologne location if you are registered as a user at ZB MED Cologne.

Article: Isolated Osseous Excision in the Adult Carpus: A Narrative Review

Dolan, Joshua D. / Shiver, Luke / Wallace, Doyle / Whitehead, Jonathon / Wood, Matthew / Fulcher, S. Mark

Journal of Hand and Microsurgery

2023

Abstract: Various pathologies of the adult carpus result in clinical scenarios where excision can be considered and even recommended. In the appropriate patient population, isolated carpal excision can alleviate pain and improve mobility. Excisions of the pisiform, ...

Abstract	Various pathologies of the adult carpus result in clinical scenarios where excision can be considered and even recommended. In the appropriate patient population, isolated carpal excision can alleviate pain and improve mobility. Excisions of the pisiform, trapezium, and trapezoid have abundant literature evidence to support positive long-term functional outcomes. In contrast, isolated excision of the capitate, hamate, and triquetrum has limited support in the literature secondary to compromise of carpal mechanics and lead to recurrent pain. Additionally, isolated scaphoid and lunate excision are best avoided secondary to carpal collapse and should be paired with concomitant stabilizing procedures in the carpus. This article provides a comprehensive literature review of isolated excision of each osseous carpal bone, their indications, and previously assessed outcomes.
Keywords	capitate ; carpal bone ; carpal excision ; lunate ; scaphoid ; trapezium ; wrist surgery
Language	English
Publishing date	2023-06-13
Publisher	Thieme Medical and Scientific Publishers Pvt. Ltd.
Publishing place	Stuttgart ; New York
Document type	Article
ISSN	0974-6897 ; 0974-3227
ISSN (online)	0974-6897
ISSN	0974-3227
DOI	10.1055/s-0043-1769748
Database	Thieme publisher's database

Order via subito

Inter-library loan at ZB MED

Your chosen title can be delivered directly to ZB MED Cologne location if you are registered as a user at ZB MED Cologne.

To top

More links

Kategorien

In stock of ZB MED Cologne/Königswinter

Order via subito

More links

Kategorien

In stock of ZB MED Cologne/Königswinter

Order via subito

More links

Kategorien

Order via subito

Inter-library loan at ZB MED

Full text online

More links

Kategorien

In stock of ZB MED Cologne/Königswinter

Order via subito

More links

Kategorien

Order via subito

More links

Kategorien

In stock of ZB MED Cologne/Königswinter

Order via subito

More links

Kategorien

In stock of ZB MED Bonn / Germany

Order via subito

Inter-library loan at ZB MED

More links

Kategorien

Order via subito

Full text online

More links

Kategorien

Inter-library loan at ZB MED

More links

Kategorien

Order via subito

Inter-library loan at ZB MED