News

Derailment of the PI3K signalling network contributes to many human diseases including cancer.

Recent work undertaken by the Alessi lab has revealed that a poorly studied kinase related to Akt termed SGK3, is recruited and activated at endosomes, by virtue of its PX domain binding to 3-phosphoinositide (PtdIns(3)P-see http://www.biochemj.org/content/463/3/413.long). Our initial data suggested that two types of phosphoinositide 3-kinase (PI3K) termed Class I and Class III were responsible for generating the PtdIns(3)P that triggered SGK3 activation.

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The University of Dundee held a special celebration for its staff members who had been in post for 25 years! Maisie Harkins (MRC-PPU lab support), Judith Hare (recently retired MRC-PPU administrator), Nicholas Helps (MRC-PPU head of DNA sequencing and health and safety) and David Campbell (head of the MRC mass spectrometry service) received a silver award from University of Dundee Principal Sir Pete Downes, for their tremendous service to MRC-PPU and University of Dundee.

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There is compelling evidence that mutations which stimulate the activity of the LRRK2 protein kinase, cause Parkinson’s disease. Orally bioavailable, brain penetrant and potent LRRK2 kinase inhibitors are in the later stages of clinical development.  There is also increasing indication that LRRK2 is over-activated in some patients with sporadic Parkinson’s disease. Therefore, there is significant need to develop a robust assay to assess LRRK2 activity in humans. 

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Mutations that activate the LRRK2 protein kinase, predispose to Parkinson’s disease, suggesting that LRRK2 inhibitors might have therapeutic benefit. Recent work has revealed that LRRK2 phosphorylates a subgroup of 14 Rab proteins, including Rab10, at a specific residue located at the centre of its effector binding Switch-II motif {see https://elifesciences.org/articles/31012}.

To analyse the activity of LRRK2 in vivo, it is essential to develop state of the art antibodies that robustly detect Rab proteins phosphorylated by LRRK2.

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Mutations that activate the Leucine-rich repeat kinase 2 (LRRK2) protein kinase, predispose to Parkinson’s disease, suggesting that LRRK2 inhibitors might have therapeutic benefit. …more

Adrien Rousseau has opened a new laboratory in the MRC PPU to investigate signalling pathways controlling proteasome homeostasis.

A major goal of Adrien’s laboratory will be to unravel the crosstalk between protein phosphorylation and ubiquitin proteasomal degradation pathways. The aim is to better understand how cells prevent accumulation of unfolded, misfolded, or damaged proteins that is deleterious and an underlying cause of various age-related diseases, including cancers and neurodegenerative disorders.

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Ying (Ivonna) Fan and Esther Sammler from the Alessi lab just returned from a visit to Professor Tolosa’s group in Barcelona, Spain where they collected clinical samples from LRRK2 mutation carriers, idiopathic Parkinson’s patients and controls. …more

Many congratulation to Dr Guadalupe Sabio, who was an PhD student with Ana Cuenda in the MRC PPU from 2003-2005, who has just been awarded a highly prestigious and sought after EMBO-YIP award. 

Guadalupe is currently an Assistant Professor in the Spanish National Centre for Cardiovascular Research, Madrid. She is undertaking important research into the role of p38 MAP Kinase pathway in the heart. 

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The University of Cambridge School of Clinical Medicine and the MRC Protein Phosphorylation and Ubiquitylation Unit (MRC PPU) have launched a new research partnership to enable clinical researchers to visit the MRC PPU for short periods to undertake mechanistic research that may aid their primary research programmes in Cambridge. …more
There is increasing interest in developing specific inhibitors to various deubiquitylases (DUBs) which are enzymes that cleave ubiquitin from substrates and are implicated in disease. Much focus has been on one of these DUBs termed ubiquitin-specific protease-7 (USP7) which regulates stability of the p53 tumour suppressor critical for tumour cell survival. Inhibitors of USP7 have the potential to stabilize p53 and other tumour suppressors and therefore inhibit tumour growth.  …more