PP2A

New Publication in Cell! The Phosphoregulation of Mitosis

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We are incredibly excited to announce that our SnapShot is out today in Cell!
This snapshot of mitosis collates hundreds of phosphorylation events and directly links them with their regulatory kinases and counterbalancing phosphatases, in both time and space, in a highly innovative ‘circtanglar’ cell layout. More importantly, the static PDF version is accompanied by an interactive website that enables users to access direct links to PubMed, UniProt, and Aquaria 3D protein structures for each and every phosphorylation event shown. The pop-up boxes also contain over 100 additional phosphorylation sites on dozens of proteins essential for mitosis. You can access the interactive web version here:  http://www.cell.com/cell/enhanced/odonoghue2
Even better news is that until August 04, 2017 the PDF version of the SnapShot is freely accessible for everyone at the following link https://authors.elsevier.com/a/1VDWh_278yyILK
A big thank-you to Jenny, Sam, Marcos and Sean for helping me put together what I hope will be an amazing resource for anyone interested in how cells divide and phosphorylation in general.

BioEssays Review on Mitotic Phosphatase Specificity now Online

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Great News, our review on how phosphatase specificity is controlled during mitosis has been re-published in BioEssays and is now Online!

This review was originally published in Inside the Cell, which unfortunately has shut down.

But the good news is that it is still Open Access, so that means its free for everyone to read! And is now also indexed in PubMed

During mitotic exit, phosphatases reverse thousands of phosphorylation events in a specific temporal order to ensure that cell division occurs correctly. This review explores how the physicochemical properties of the phosphosite and surrounding amino acids affect interactions with phosphatase/s and help determine the dephosphorylation of individual phosphorylation sites during mitotic exit.

The Full-text download for the Article can be found here [Link]

Citation: Rogers, S. et al. (2016) Mechanisms regulating phosphatase specificity and the removal of individual phosphorylation sites during mitotic exit. BioEssays, 38, S24–S32.

 

Switching off Cancers Diversity

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JCS paper

A defining feature in over 2/3rds of all solid tumours is the continual loss and gain of whole are small parts of chromosomes. This instability, or CIN for short, strongly implicated in tumour initiation, progression, chemoresistance and poor prognosis. CIN is created through failures during mitosis, whereby whole or parts of a chromosome are segregated incorrectly, thereby created daughter cells with unequal chromosome numbers. Consequently, understanding how mitosis is regulated is essential for uncovering the mechanisms allowing CIN to arise and drive cancer. In our recent publication, we discovered the mechanisms controlling the key regulatory pathway critical to ensuring cells exit mitosis correctly. At the centre of this pathway is a gene call MASTL (short for ‘Microtubule Associated Serine/Threonine Kinase-Like’). The primary function of MASTL is to ensure that the cellular breaks (the phosphatase PP2A), is turned off during mitosis so that the accelerator (Cdk1 kinase) can drive the cell into mitosis. Much like a car, having the accelerator and breaks on at the same time is a bad idea, unless you like the smell of burning rubber. To successfully exit mitosis, and to perfectly segregate chromosomes, the cell must take the foot off the accelerator and turn on the breaks. Because MASTL is the central regulator ensuring the breaks are coordinated with the accelerator, it is essential to understand how MASTL is controlled. To this end, we uncovered that MASTL must be rapidly turned off to allow cells to exit mitosis, and this inactivation is carried out by another cellular brake call PP1 phosphatase (Rogers et al, JCS 2016). Now that we have identified and mapped this novel mitotic exit switch, we hope to be able to shed new light on how CIN drives the initiation and evolution cancer. We believe that with further study we will be able to better predict patient response to chemotherapy, and also identify new ways to ‘switch off’ highly unstable tumours, thereby improving treatment for patients that currently have a very poor prognosis.

Image of Interphase HeLa cell stained for Actin (red), DNA (blue) and the co-localisation of MASTL and PP1 by Proximity Ligation Assay (PLA; green).
Credit: Sam Rogers and Cell Division Lab

 

New Review Article Published!! “Mechanisms Regulating Phosphatase Specificity During Mitotic Exit”

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Great News, we have a new review article that has just been published online today in Inside the Cell!
Its Open Access, so that means its free for everyone to read!

During mitotic exit, phosphatases reverse thousands of phosphorylation events in a specific temporal order to ensure that cell division occurs correctly. This review explores how the physicochemical properties of the phosphosite and surrounding amino acids affect interactions with phosphatase/s and help determine the dephosphorylation of individual phosphorylation sites during mitotic exit.

The Full Reference and link for the Article can be found below:
Samuel Rogers, Rachael McCloy, D Neil Watkins and Andrew Burgess Mechanisms regulating phosphatase specificity and the removal of individual phosphorylation sites during mitotic exit Inside the Cell [Link]

New Paper Published! More data on the global phosphorylation changes during early mitotic exit

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Figure 1

Great news, we have another publication. This time its some extra data left over from our large mass spectrometry study we published in August in Molecular & Cellular Proteomics.

This latest work we provide additional analysis of our large proteomics dataset and identify motifs that correlated strongly with phosphorylation status for each of the major mitotic kinases.

These motifs could be used to predict the stability of phosphorylated residues in proteins of interest, and help infer potential functional roles for uncharacterized phosphorylations.

If you would like more information you can check out the full paper here [Link]. And the great news is that its OpenAccess and FREE for everyone!

Rogers, S., McCloy, R. A., Parker, B. L., Chaudhuri, R., Gayevskiy, V., Hoffman, N. J., Watkins, D. N., Daly, R. J., James, D. E., and Burgess, A. (2015) Dataset from the global phosphoproteomic mapping of early mitotic exit in human cells. Data in Brief 5, 45–52

 

 

 

Our Latest Publication Accepted and Now Online!

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Great news our latest publication “Global phosphoproteomic mapping of early mitotic exit in human cells identifies novel substrate dephosphorylation motifs” has been accepted by the top Proteomics Journal Molecular & Cellular Proteomics.

You can currently download the unformatted version for free here [link]

And here is an still image from the paper showing live HeLa cells undergoing forced phosphatase dependent mitotic exit. The red colour is Histone H2B tagged with the fluorescent mCherry protein, and the Green is tubulin tagged with GFP (green fluorescent protein).

 

HeLa cells undergoing phosphatase dependent mitotic exit
HeLa cells undergoing phosphatase dependent mitotic exit

 

Were the front cover feature image on this months issue of Cell Cycle !

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Some more good news to coincide with today’s official release of our manuscript, one of our images has been chosen to be the feature image on the front cover.

It’s a great honour, one that I am very proud of, and is the first time I have ever had a front cover !
You can view the current issue (Volume 13 – Issue 9 – May 1, 2014) here.

Or jump directly to our paper here

Front Cover 

FrontCoverCC13-9

 

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