The Ubiquitin System for Protein Degradation and Some of Its Roles in the Control of the Cell-Division Cycle (Nobel Lecture)

2005 ◽  
Vol 44 (37) ◽  
pp. 5932-5943 ◽  
Author(s):  
Avram Hershko
Keyword(s):  
Cell Division ◽  
Protein Degradation ◽  
Cell Division Cycle ◽  
Nobel Lecture ◽  
Ubiquitin System

scholarly journals Proteasome-mediated protein degradation resets the cell division cycle and triggers ESCRT-III-mediated cytokinesis in an archaeon

2019 ◽  
Author(s):  
Gabriel Tarrason Risa ◽  
Fredrik Hurtig ◽  
Sian Bray ◽  
Anne E. Hafner ◽  
Lena Harker-Kirschneck ◽  
...  
Keyword(s):  
Cell Division ◽  
Protein Degradation ◽  
Division Ring ◽  
Cell Division Cycle ◽  
Sulfolobus Acidocaldarius ◽  
State Dependent

AbstractThe archaeon Sulfolobus acidocaldarius is a relative of eukaryotes known to progress orderly through its cell division cycle despite lacking obvious CDK/cyclin homologues. Here, in exploring the mechanisms underpinning archaeal cell division cycle control, we show that the proteasome of S. acidocaldarius, like its eukaryotic counterpart, regulates the transition from the end of one cell division cycle to the beginning of the next. Further, we identify the archaeal ESCRT-III homologue CdvB as a key target of the proteasome, and show that state-dependent degradation of CdvB triggers archaeal cell division by allowing constriction of a CdvB1:CdvB2 ESCRT-III division ring. These findings suggest an ancient role for proteasome-mediated degradation in resetting the cell division cycle in both archaea and eukaryotes.

Regulation of genes for the cdc25 phosphatases is important for checkpoint control during the cell division cycle

2001 ◽  
Vol 120 (5) ◽  
pp. A501-A501
Author(s):  
U HAUGWITZ ◽  
M WIEDMANN ◽  
K SPIESBACH ◽  
K ENGELAND ◽  
J MOSSNER
Keyword(s):  
Cell Division ◽  
Cell Division Cycle ◽  
Checkpoint Control

scholarly journals A Molecular Modeling Approach to Identify Potential Antileishmanial Compounds Against the Cell Division Cycle (cdc)-2-Related Kinase 12 (CRK12) Receptor of Leishmania donovani

Biomolecules ◽  
2021 ◽  
Vol 11 (3) ◽  
pp. 458
Author(s):  
Emmanuel Broni ◽  
Samuel K. Kwofie ◽  
Seth O. Asiedu ◽  
Whelton A. Miller ◽  
Michael D. Wilson
Keyword(s):  
Natural Products ◽  
Cell Division ◽  
Leishmania Donovani ◽  
Therapeutic Potential ◽  
Neglected Tropical Diseases ◽  
Binding Pocket ◽  
Cell Division Cycle ◽  
World Health ◽  
Atp Binding ◽  
African Flora

The huge burden of leishmaniasis caused by the trypanosomatid protozoan parasite Leishmania is well known. This illness was included in the list of neglected tropical diseases targeted for elimination by the World Health Organization. However, the increasing evidence of resistance to existing antimonial drugs has made the eradication of the disease difficult to achieve, thus warranting the search for new drug targets. We report here studies that used computational methods to identify inhibitors of receptors from natural products. The cell division cycle-2-related kinase 12 (CRK12) receptor is a plausible drug target against Leishmania donovani. This study modelled the 3D molecular structure of the L. donovani CRK12 (LdCRK12) and screened for small molecules with potential inhibitory activity from African flora. An integrated library of 7722 African natural product-derived compounds and known inhibitors were screened against the LdCRK12 using AutoDock Vina after performing energy minimization with GROMACS 2018. Four natural products, namely sesamin (NANPDB1649), methyl ellagic acid (NANPDB1406), stylopine (NANPDB2581), and sennecicannabine (NANPDB6446) were found to be potential LdCRK12 inhibitory molecules. The molecular docking studies revealed two compounds NANPDB1406 and NANPDB2581 with binding affinities of −9.5 and −9.2 kcal/mol, respectively, against LdCRK12 which were higher than those of the known inhibitors and drugs, including GSK3186899, amphotericin B, miltefosine, and paromomycin. All the four compounds were predicted to have inhibitory constant (Ki) values ranging from 0.108 to 0.587 μM. NANPDB2581, NANPDB1649 and NANPDB1406 were also predicted as antileishmanial with Pa and Pi values of 0.415 and 0.043, 0.391 and 0.052, and 0.351 and 0.071, respectively. Molecular dynamics simulations coupled with molecular mechanics Poisson–Boltzmann surface area (MM/PBSA) computations reinforced their good binding mechanisms. Most compounds were observed to bind in the ATP binding pocket of the kinase domain. Lys488 was predicted as a key residue critical for ligand binding in the ATP binding pocket of the LdCRK12. The molecules were pharmacologically profiled as druglike with inconsequential toxicity. The identified molecules have scaffolds that could form the backbone for fragment-based drug design of novel leishmanicides but warrant further studies to evaluate their therapeutic potential.

scholarly journals Targeting Cell Division Cycle 25 Homolog B To Regulate Influenza Virus Replication

2013 ◽  
Vol 87 (24) ◽  
pp. 13775-13784 ◽  
Author(s):  
O. Perwitasari ◽  
A. C. Torrecilhas ◽  
X. Yan ◽  
S. Johnson ◽  
C. White ◽  
...  
Keyword(s):  
Influenza Virus ◽  
Cell Division ◽  
Virus Replication ◽  
Cell Division Cycle ◽  
Influenza Virus Replication

Cell division cycle control in embryonal and alveolar rhabdomyosarcomas

2002 ◽  
Vol 38 (17) ◽  
pp. 2290-2299 ◽  
Author(s):  
A Moretti ◽  
A Borriello ◽  
F Monno ◽  
M Criscuolo ◽  
A Rosolen ◽  
...  
Keyword(s):  
Cell Division ◽  
Cell Division Cycle
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