Theresa Zeisner

A chemical-genetic system to rapidly inhibit the PP2A-B56 phosphatase reveals a role at metaphase kinetochores - Nature Communications Phosphatase enzymes are challenging to study due to a lack of specific inhibitors. Here, authors develop a chemical-genetic system to inhibit and characterize a major Ser/Thr phosphatase complex, and ...

Delighted to share a chemical-genetic system we developed to rapidly inhibit a serine/threonine phosphatase complex (within secs). This will make it much easier to study #phosphatases. The system is also applicable to other “undruggable” enzymes.

www.nature.com/articles/s41...

Thrilled to announce that I am looking for a Research Technician/Assistant to join my lab @imbavienna.bsky.social. Please consider applying if you’re enthusiastic about #devbio #stemcells #teamwork and excited to help shaping a new lab!

Thankful for any retweet! 🫶

imba.onlyfy.jobs/job/l6u2m980

We have a 4-year PhD-student opening in our lab, deadline on Wednesday noon.

For anyone interested in computational genomics of ancient human, pathogen, or canid genomes. www.crick.ac.uk/careers-stud...

If you are curious, send in an application!

openRxiv has arrived!

We’re thrilled to announce the launch of openRxiv as an independent, researcher-led nonprofit to oversee bioRxiv and medRxiv, the world’s leading preprint servers for life and health sciences.
openrxiv.org/introducing-...

#openRxiv #OpenScience #Preprints #bioRxiv #medRxiv

Just under two weeks left to apply for PhD positions at the Crick 🔬🧬 Check out this video featuring @sarahwillich.bsky.social for some application tips youtu.be/XjW4LqwKNFs

Big thanks to Tania for her phospho-expertise and the entire Nurse lab (past and present) for their support, comments and discussions! 🌟

Without PP2A-B55 or CDC14 cells enter mitosis earlier

This advance is independent of CDK activity regulation. This indicates that in the absence of these Ppases, critical CDK substrates can be phosphorylated at lower CDK activity levels (ie earlier), thus advancing mitotic entry.

What happens in the absence of the Ppases?

Using a fluorescent sensor, we showed that without PP2A-B55, a candidate substrate (Cut3-T19) is phosphorylated earlier and less rapidly.

This suggests that the identity of the Ppase that targets a CDK substrate site affects its phosphorylation timing. The exact phosphorylation timing of a given site is determined by a combination of factors.

Does the division of labour between the Ppase impact the timing of CDK substrate phosphorylation? Yes! ✅

Phosphoproteomic timecourse showed that CDK substrates targeted by CDC14 and PP2A-B56 are, on average, net phosphorylated first, followed by CDK substrates targeted by PP1 and then PP2A-B55.

Identifying some more Ppase substrates…

We also identified 3,000+ Ppase substrates phosphorylated by other kinases (not CDK). The identified Ppase motifs were similar to those identified in other eukaryotes, indicating conservation of Ppase substrate specificity.

Distinct Ppase targets

• PP2A-B55, B56, CDC14 & PP1 targeted specific subgroups of CDK sites
• <5% of sites were targeted by multiple Ppases
• Ppases had different preferences for amino acids

🔎 Identifying Ppase substrates

We used phosphoproteomics: inhibiting CDK with & without Ppase and tracking dephosphorylation. We classified a site as a Ppase substrate if it was dephosphorylated substantially slower in the absence of the Ppase.

❓Open questions

How do CDK-opposing Ppases (PP2A-B55, PP2A-B56, PP1 & CDC14) together influence the phosphorylation timing of CDK substrates?
To answer this, we first needed to identify which CDK substrate is targeted by which Ppase.

🔄 CDK-opposing Ppases

• Important at mitotic exit to dephosphorylate CDK substrates
• Ppases are also active during interphase ➡️ could affect phosphorylation timing
• But for the majority of CDK substrate sites, it is not known which Ppase targets it

⏰ The cell cycle is driven by reversible phosphorylations

Hundreds of proteins need to be phosphorylated at the right time by cyclin-dependent kinases (CDKs) to order cell cycle events. These phosphorylations are opposed by phosphatases (Ppases), such as PP2A-B55, PP2A-B56, PP1 & CDC14.

🚨New preprint🚨

How do phosphatases affect CDK substrate phosphorylation timing during the cell cycle?

We showed that substrates dephosphorylated by different Ppases are net phosphorylated at different times.

📖 Read here: doi.org/10.1101/2025... & follow along for some key insights 🧵

Home We’ve got loads of science experiments, quizzes and crafts for kids and families. Get exploring and see what you discover on Crick Kids.

🧪 Got a curious 7–11 year-old at home? 🔍 Whether they’re wondering how yeast grows or want to craft some red blood cells, the new Crick Kids website has them covered! 🎉

Discover fun science activities, hands-on experiments, and lots of quizzes 🧬👩‍🔬🔬

👉 Check it out here: kids.crick.ac.uk

Conference announcement Join us in Liverpool to celebrate our 100th anniversary Biologists @ 100 24-27 March 2025, ACC Liverpool, UK biologists.com/100-years/conference Register now Extended abstract deadline: 17 January 2025 #biologists100

🧪The deadline to submit an abstract for oral and poster presentations at our Biologists @ 100 conference has been extended to Friday 17 January 2025. View the abstract topics and submit yours at 100yearsconference.biologists.com/abstracts/ #biologists100

PhosX is out! doi.org/10.1093/bioi... Leveraging the latest kinase specificity maps by the Cantley, Yaffe, and Turk labs and a rank sum statistic we created PhosX so now we can predict activities for nearly all kinases in your phosphodata, including the understudied ones. Check it out!