Thomas Macartney

NEK1 autophosphorylation is disrupted by amyotrophic lateral sclerosis-associated missense variants: activity biomarkers and structural insights

Kinase-dead controls, XIC quantification and phosphospecific antibodies establish pSer14, pThr156 and pSer418 as NEK1 autophosphorylation sites; a pThr156 assay shows ALS missense variants differ, with R261C reducing it most.

Data-independent acquisition (DIA) approach for comprehensive ubiquitinome profiling in targeted protein degradation

This study develops a DIA-based workflow for comprehensive ubiquitinome profiling in targeted protein degradation, identifying over 40,000 ubiquitylated peptides.

Targeted dephosphorylation of Tau at the endogenous level promotes its association with microtubules.

This study shows targeted dephosphorylation of phospho-Tau at the endogenous level promotes its association with microtubules.

A PLK1-Directed Mitotic Genome Maintenance Network Promotes DNA Synthesis in Mitosis

This study identifies PLK1-associated DNA repair factors and shows PLK1's role in mitotic DNA synthesis through specific interactions with SLX4 and RAD52.

The contribution of native protein complexes to targeted protein degradation

This study shows that molecular glue degraders targeting CK1 can co-degrade multiple SACK1 proteins, highlighting the role of protein complex context in targeted protein degradation.

Mutations within the predicted fragment-binding region of FAM83G/SACK1G abolish its interaction with the Ser/Thr kinase CK1α

The paper identifies mutations in SACK1G that disrupt its interaction with CK1α, using computational modeling and experimental validation.

HMMR/RHAMM recruits SACK1D/FAM83D-CK1α complex at the mitotic spindle to control spindle alignment

This study identifies HMMR's role in stabilizing the SACK1D-CK1 complex at the mitotic spindle and shows how phosphorylation drives its degradation after mitosis.

Phosphorylation enables progressive microtubule-associated protein proteolysis and functionalisation during neural development

The paper identifies SRPK-mediated phosphorylation of MAP1S, showing it regulates proteolytic processing and microtubule binding during neurodevelopment.

NOTCH1 S2513 is critical for the regulation of NICD levels impacting the segmentation clock in hiPSC-derived PSM cells and somitoids

This study shows that a NOTCH1 mutation affects NICD stability and disrupts segmentation clock function in hiPSC-derived PSM cells and somitoids.

NRBP1 pseudokinase binds to and activates the WNK pathway in response to osmotic stress

This study identifies NRBP1 as an upstream activator of the WNK pathway by forming a multi-subunit complex with WNK1, SPAK, and TSC22D4 in response to osmotic stress.

Targeted degradation of α-synuclein prevents PFF-induced aggregation

This study demonstrates targeted degradation of α-synuclein using a nanobody-guided system, preventing PFF-induced aggregation in neurons.

Parkinsons VPS35 mutation induces LRRK2 mediated lysosomal association of RILPL1 and TMEM55B

This study shows that the VPS35[D620N] mutation causes lysosomal dysfunction, activates LRRK2, and promotes the lysosomal association of RILPL1 and TMEM55B through phosphorylation of Rab proteins.

Functional diversification of Ser-Arg rich protein kinases to control ubiquitin-dependent neurodevelopmental signalling

The paper shows SRPK regulates ubiquitin-dependent neurodevelopmental signalling by phosphorylating RNF12, linking SRPK mutations to intellectual disability.

Targeting endogenous K-RAS for degradation through the affinity-directed protein missile system

This paper demonstrates the degradation of endogenous K-RAS and H-RAS using an AdPROM system, offering a new approach for targeting undruggable cancer proteins.