metaphase

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.
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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.

 

AntiOxidants and Cancer: A complicated story

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A recent high profile publication in Science Translational Medicine proposed that antioxidants might increase the rate of metastasis in mice models of melanoma.

NAC and the soluble vitamin E analog Trolox markedly increased the migration and invasive properties of human malignant melanoma cells but did not affect their proliferation. Both antioxidants increased the ratio between reduced and oxidized glutathione in melanoma cells and in lymph node metastases, and the increased migration depended on new glutathione synthesis. Furthermore, both NAC and Trolox increased the activation of the small guanosine triphosphatase (GTPase) RHOA, and blocking downstream RHOA signaling abolished antioxidant-induced migration. These results demonstrate that antioxidants and the  system play a previously unappreciated role in malignant melanoma progression.

This goes against the common idea that anti-oxidants are cancer fighters!

So what is going on?

The answer, much like a Facebook relationship status, is “its complicated”. In fact anti-oxidants can have a wide range of effects on cells, including mitosis. Many “dietary antioxidants Resveratrol and Fisetin (found in red wine), inhibit Cdks, induce a G2 arrest and prevent entry into mitosis” (Burgess et al 2014). Furthermore, we recently showed that partial inhibition of Cdk1 can dramatically disrupt to mitosis. This caused increase cancer cell death… but also increased the rate of chromosome mis-segergations. (McCloy et al 2014). These mitotic errors can drive chromosome instability (CIN), which inturn can lead to the evolution of more aggressive, invasive tumours. Understanding the genetic background of each individual cancer will be key to determining why some cancer cells die and others thrive when given antioxidants.

If you would like to know more on how common stresses such as oxidation can disrupt mitosis, you can read our recent review Stressing Mitosis to Death.

Until then, if you have cancer and are thinking of taking antioxidants, make sure you consult your oncologist as they can significantly affect the efficacy of some chemotherapeutics, and hence maybe doing more harm than good.

 

 

 

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

 

We will be at the Sydney Light Optical Users Meeting on July 24th 2014

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Great news, Cell Division Lab will be at the  Sydney Light Optical Users Meeting, hosted by Dr Pamela Young at Sydney University, this Thursday (24th of July).

I will be presenting a short seminar on “Imaging and Analysing Cell Division”.

If you would like to attend please contact Pamela asap. Her details are below!

Hope to see you there !

Sydney Light Optical Users Meeting July 2014

Our Latest Review Article “Stressing Mitosis to Death” is now online !

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Great news, our latest review article “Stressing Mitosis to Death” has been accepted for publication by Frontiers in Oncology. You can access the provisional pre-press version here.

The review is about how common stresses affect mitosis, and the impact these stresses can have on the blockbuster mitotic chemotherapy drug Taxol (paclitaxel)

Finally here is one of the beautiful figures drawn by our own Sam Rogers for the Review!  Hope you enjoy the read !

 

Fig. v4

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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Cell Image of the Week – Mitotic Catastrophe

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Here is one of the images that we took using a Leica SP8 confocal microscope this week in the lab.
It is a 3D image of a HeLa cell that has completely stuffed up mitosis (undergone mitotic catastrophe). It has separated whole chromosomes randomly into 2 daughter cells instead of separating the two identical chromatids in two.

And here is an artistic version just for fun !