scholarly journals Phylogenetic Analyses of Proteins Coordinating G2 Size Control in Fission Yeast

Author(s):  
Zsófia Nagy ◽  
Anna Medgyes-Horváth ◽  
Csilla Szalay ◽  
Matthias Sipiczki ◽  
Ákos Sveiczer

Regulation of G2 phase is based on inhibition of MPF (M-phase Promoting Factor) through phosphorylation by Wee1-like kinases. Removal of the inhibiting phosphate group requires Cdc25-like phosphatases. In fission yeast, size control is achieved by monitoring cell length via interactions of Pom1, Nif1, Cdr1 and Cdr2 proteins, regulating MPF via the Wee1 kinase. Here, a search for homologues of these key proteins was performed in the genomes of several model organisms to analyze the evolution of G2 size control. Both the known upstream pathways regulating Wee1 protein (Pom1 → Cdr2, and Nif1 → Cdr1) have been found to be characteristic only in fission yeasts. Mik1, a backup copy of Wee1 kinase probably appeared in the common ancestor of the fission yeasts. The duplication resulting in Wee1A and Wee1B isoforms probably happened in a common ancestor of higher animals, while the Myt1 protein (found only in animals) could be a variant between an ancient serine / threonine kinase and the Wee1 tyrosine kinase. Probably both the ancestors of plants and that of fungi may have lost the myt1 gene. In fission yeasts, Pyp3 is a backup phosphatase of Cdc25, also activating MPF in late G2. Interestingly, we found that the small Ibp1 phosphatase appeared to be a closer homologue of Cdc25, although its function is different. Moreover, Cdc25 homologues identified in plants were found to be more closely related to Ibp1 rather than to Cdc25 of fission yeast. In the Cdc25-like proteins, a novel conserved region was found with the consensus sequence LxxG(Y/F).

FEBS Letters ◽  
2002 ◽  
Vol 524 (1-3) ◽  
pp. 79-86 ◽  
Author(s):  
Vicenç Alemany ◽  
Maribel Sanchez-Piris ◽  
Oriol Bachs ◽  
Rosa Aligue

2020 ◽  
Vol 77 (22) ◽  
pp. 4693-4708 ◽  
Author(s):  
Sihyeon An ◽  
Oh Sung Kwon ◽  
Jinbae Yu ◽  
Sung Key Jang

Abstract During mitosis, translation of most mRNAs is strongly repressed; none of the several explanatory hypotheses suggested can fully explain the molecular basis of this phenomenon. Here we report that cyclin-dependent CDK11/p58—a serine/threonine kinase abundantly expressed during M phase—represses overall translation by phosphorylating a subunit (eIF3F) of the translation factor eIF3 complex that is essential for translation initiation of most mRNAs. Ectopic expression of CDK11/p58 strongly repressed cap-dependent translation, and knockdown of CDK11/p58 nullified the translational repression during M phase. We identified the phosphorylation sites in eIF3F responsible for M phase-specific translational repression by CDK11/p58. Alanine substitutions of CDK11/p58 target sites in eIF3F nullified its effects on cell cycle-dependent translational regulation. The mechanism of translational regulation by the M phase-specific kinase, CDK11/p58, has deep evolutionary roots considering the conservation of CDK11 and its target sites on eIF3F from C. elegans to humans.


2019 ◽  
Vol 19 (2) ◽  
pp. 326-343 ◽  
Author(s):  
Dario Hermida ◽  
Gulnahar B. Mortuza ◽  
Anna-Kathrine Pedersen ◽  
Irina Pozdnyakova ◽  
Tam T. T. N. Nguyen ◽  
...  

The human MASTL (Microtubule-associated serine/threonine kinase-like) gene encodes an essential protein in the cell cycle. MASTL is a key factor preventing early dephosphorylation of M-phase targets of Cdk1/CycB. Little is known about the mechanism of MASTL activation and regulation. MASTL contains a non-conserved insertion of 550 residues within its activation loop, splitting the kinase domain, and making it unique. Here, we show that this non-conserved middle region (NCMR) of the protein is crucial for target specificity and activity. We performed a phosphoproteomic assay with different MASTL constructs identifying key phosphorylation sites for its activation and determining whether they arise from autophosphorylation or exogenous kinases, thus generating an activation model. Hydrogen/deuterium exchange data complements this analysis revealing that the C-lobe in full-length MASTL forms a stable structure, whereas the N-lobe is dynamic and the NCMR and C-tail contain few localized regions with higher-order structure. Our results indicate that truncated versions of MASTL conserving a cryptic C-Lobe in the NCMR, display catalytic activity and different targets, thus establishing a possible link with truncated mutations observed in cancer-related databases.


2001 ◽  
Vol 152 (2) ◽  
pp. 275-288 ◽  
Author(s):  
Akira Kawasaki ◽  
Itaru Matsumura ◽  
Jun-ichiro Miyagawa ◽  
Sachiko Ezoe ◽  
Hirokazu Tanaka ◽  
...  

During the late phase of megakaryopoiesis, megakaryocytes undergo polyploidization, which is characterized by DNA duplication without concomitant cell division. However, it remains unknown by which mechanisms this process occurs. AIM-1 and STK15 belong to the Aurora/increase-in-ploidy (Ipl)1 serine/threonine kinase family and play key roles in mitosis. In a human interleukin-3–dependent cell line, F-36P, the expressions of AIM-1 and STK15 mRNA were specifically observed at G2/M phase of the cell cycle during proliferation. In contrast, the expressions of AIM-1 and STK15 were continuously repressed during megakaryocytic polyploidization of human erythro/megakaryocytic cell lines (F-36P, K562, and CMK) treated with thrombopoietin, activated ras (H-rasG12V), or phorbol ester. Furthermore, their expressions were suppressed during thrombopoietin-induced polyploidization of normal human megakaryocytes. Activation of AIM-1 by the induced expression of AIM-1(wild-type) canceled TPA-induced polyploidization of K562 cells significantly, whereas that of STK15 did not. Moreover, suppression of AIM-1 by the induced expression of AIM-1 (K/R, dominant-negative type) led to polyploidization in 25% of K562 cells, whereas STK15(K/R) showed no effect. Also, the induced expression of AIM-1(K/R) in CMK cells provoked polyploidization up to 32N. These results suggested that downregulation of AIM-1 at M phase may be involved in abortive mitosis and polyploid formation of megakaryocytes.


1993 ◽  
Vol 21 (17) ◽  
pp. 4079-4083 ◽  
Author(s):  
Suresh K. Alahari ◽  
Henning Schmidt ◽  
Norbert F. Kaufer

1997 ◽  
Vol 272 (45) ◽  
pp. 28646-28651 ◽  
Author(s):  
Bin Ouyang ◽  
Huiqi Pan ◽  
Luo Lu ◽  
Jian Li ◽  
Peter Stambrook ◽  
...  

2002 ◽  
Vol 277 (20) ◽  
pp. 17722-17727 ◽  
Author(s):  
Maribel Sánchez-Piris ◽  
Francesc Posas ◽  
Vicenç Alemany ◽  
Ingeborg Winge ◽  
Elena Hidalgo ◽  
...  

2015 ◽  
Vol 53 (12) ◽  
Author(s):  
J Wohlfahrt ◽  
A Fettelschoss ◽  
T Kündig ◽  
H Hermanns ◽  
B Müllhaupt ◽  
...  

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