scholarly journals Rac1 accumulates in the nucleus during the G2 phase of the cell cycle and promotes cell division

2008 ◽  
Vol 181 (3) ◽  
pp. 485-496 ◽  
Author(s):  
David Michaelson ◽  
Wasif Abidi ◽  
Daniele Guardavaccaro ◽  
Mo Zhou ◽  
Ian Ahearn ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Cell Division ◽  
Time Lapse ◽  
Subcellular Fractionation ◽  
Mitotic Rate ◽  
Nuclear Localization Sequence ◽  
Cellular Processes ◽  
C Terminus ◽  
Localization Sequence ◽  
Polybasic Region

Rac1 regulates a wide variety of cellular processes. The polybasic region of the Rac1 C terminus functions both as a plasma membrane–targeting motif and a nuclear localization sequence (NLS). We show that a triproline N-terminal to the polybasic region contributes to the NLS, which is cryptic in the sense that it is strongly inhibited by geranylgeranylation of the adjacent cysteine. Subcellular fractionation demonstrated endogenous Rac1 in the nucleus and Triton X-114 partition revealed that this pool is prenylated. Cell cycle–blocking agents, synchronization of cells stably expressing low levels of GFP-Rac1, and time-lapse microscopy of asynchronous cells revealed Rac1 accumulation in the nucleus in late G2 and exclusion in early G1. Although constitutively active Rac1 restricted to the cytoplasm inhibited cell division, activated Rac1 expressed constitutively in the nucleus increased the mitotic rate. These results show that Rac1 cycles in and out of the nucleus during the cell cycle and thereby plays a role in promoting cell division.

scholarly journals Regulation of cell cycle drivers by Cullin-RING ubiquitin ligases

2020 ◽  
Vol 52 (10) ◽  
pp. 1637-1651 ◽  
Author(s):  
Sang-Min Jang ◽  
Christophe E. Redon ◽  
Bhushan L. Thakur ◽  
Meriam K. Bahta ◽  
Mirit I. Aladjem
Keyword(s):  
Cell Cycle ◽  
Cell Division ◽  
Cell Cycle Progression ◽  
Ubiquitin Ligases ◽  
Anaphase Promoting Complex ◽  
Cycle Progression ◽  
Cellular Processes ◽  
Cellular Pathways ◽  
Regulation Of Cell Cycle ◽  
F Box Protein

Abstract The last decade has revealed new roles for Cullin-RING ubiquitin ligases (CRLs) in a myriad of cellular processes, including cell cycle progression. In addition to CRL1, also named SCF (SKP1-Cullin 1-F box protein), which has been known for decades as an important factor in the regulation of the cell cycle, it is now evident that all eight CRL family members are involved in the intricate cellular pathways driving cell cycle progression. In this review, we summarize the structure of CRLs and their functions in driving the cell cycle. We focus on how CRLs target key proteins for degradation or otherwise alter their functions to control the progression over the various cell cycle phases leading to cell division. We also summarize how CRLs and the anaphase-promoting complex/cyclosome (APC/C) ligase complex closely cooperate to govern efficient cell cycle progression.

scholarly journals The midregion, nuclear localization sequence, and C terminus of PTHrP regulate skeletal development, hematopoiesis, and survival in mice

2010 ◽  
Vol 24 (6) ◽  
pp. 1947-1957 ◽  
Author(s):  
Ramiro E. Toribio ◽  
Holly A. Brown ◽  
Chad M. Novince ◽  
Brandlyn Marlow ◽  
Krista Hernon ◽  
...  
Keyword(s):  
Nuclear Localization ◽  
Skeletal Development ◽  
Nuclear Localization Sequence ◽  
C Terminus ◽  
Localization Sequence

scholarly journals PTHrP Nuclear Localization and Carboxyl Terminus Sequences Modulate Dental and Mandibular Development in Part via the Action of p27

Endocrinology ◽  
2016 ◽  
Vol 2016 (1) ◽  
pp. 72-84 ◽  
Author(s):  
Wen Sun ◽  
Jun Wu ◽  
Linying Huang ◽  
Hong Liu ◽  
Rong Wang ◽  
...  
Keyword(s):  
Nuclear Localization ◽  
Alveolar Bone ◽  
Bone Volume ◽  
Carboxyl Terminus ◽  
Nuclear Localization Sequence ◽  
Wild Type ◽  
Mineral Density ◽  
C Terminus ◽  
Localization Sequence ◽  
Dentin Sialoprotein

Abstract To determine whether the action of the PTHrP nuclear localization sequence and C terminus is mediated through p27 in modulating dental and mandibular development, compound mutant mice, which are homozygous for both p27 deletion and the PTHrP1–84 knock-in mutation (p27−/−PthrpKI/KI), were generated. Their teeth and mandibular phenotypes were compared with those of p27−/−, PthrpKUK\ and wild-type mice. At 2 weeks of age, the mandibular mineral density, alveolar bone volume, osteoblast numbers, and dental volume, dentin sialoprotein-immunopo-sitive areas in the first molar were increased significantly in p27−/− mice and decreased dramatically in both PthrpKI/KI and p27−/− PthrpKI/KI mice compared with wild-type mice; however, these parameters were partly rescued in p27−/− PthrpKI/KI mice compared with PthrpKI/KI mice. These data demonstrate that the deletion of p27 in PthrpKI/KI mice can partially rescue defects in dental and mandibular development. Furthermore, we found that deletion of p27 in PthrpKI/KI mice partially corrected the dental and mandibular phenotype by modulating cell cyclin-regulating molecules and antioxidant enzymes. This study therefore indicates that the p27 pathway may function downstream in the action of PTHrP nuclear localization sequence to regulate dental and mandibular development. (Endocrinology 157: 1372–1384, 2016)

scholarly journals Cyclin D-Cdk4,6 drives cell cycle progression via the retinoblastoma protein’s C-terminal helix

2018 ◽  
Author(s):  
Benjamin R. Topacio ◽  
Evgeny Zatulovskiy ◽  
Sandra Cristea ◽  
Shicong Xie ◽  
Carrie S. Tambo ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Cell Division ◽  
Cell Cycle Progression ◽  
Alpha Helix ◽  
G1 Arrest ◽  
Cyclin D ◽  
Cycle Progression ◽  
C Terminus ◽  
Docking Mechanism ◽  
Tumor Suppressive Function

SummaryThe cyclin-dependent kinases Cdk4 and Cdk6 form complexes with D-type cyclins to drive cell proliferation. A well-known target of cyclin D-Cdk4,6 is the retinoblastoma protein, Rb, which inhibits cell cycle progression until its inactivation by phosphorylation. However, the role of cyclin D-Cdk4,6 phosphorylation of Rb in cell cycle progression is unclear because Rb can be phosphorylated by other cyclin-Cdk complexes and cyclin D-Cdk4,6 complexes have other targets that may drive cell division. Here, we show that cyclin D-Cdk4,6 docks one side of an alpha-helix in the C-terminus of Rb, which is not recognized by cyclins E, A, and B. This helix-based docking mechanism is shared by the p107 and p130 Rb-family members across metazoans. Mutation of the Rb C-terminal helix prevents phosphorylation, promotes G1 arrest, and enhances Rb’s tumor suppressive function. Our work conclusively demonstrates that the cyclin D-Rb interaction drives cell division and defines a new class of cyclin-based docking mechanisms.

scholarly journals Instructive simulation of the bacterial cell division cycle

Microbiology ◽  
2011 ◽  
Vol 157 (7) ◽  
pp. 1876-1885 ◽  
Author(s):  
Arieh Zaritsky ◽  
Ping Wang ◽  
Norbert O. E. Vischer
Keyword(s):  
Cell Cycle ◽  
Cell Division ◽  
Dna Replication ◽  
Cell Mass ◽  
Time Lapse ◽  
Replication Initiation ◽  
Bacterial Cells ◽  
Bacterial Cell Division ◽  
Cycle Simulation ◽  
New Ideas

The coupling between chromosome replication and cell division includes temporal and spatial elements. In bacteria, these have globally been resolved during the last 40 years, but their full details and action mechanisms are still under intensive study. The physiology of growth and the cell cycle are reviewed in the light of an established dogma that has formed a framework for development of new ideas, as exemplified here, using the Cell Cycle Simulation (CCSim) program. CCSim, described here in detail for the first time, employs four parameters related to time (replication, division and inter-division) and size (cell mass at replication initiation) that together are sufficient to describe bacterial cells under various conditions and states, which can be manipulated environmentally and genetically. Testing the predictions of CCSim by analysis of time-lapse micrographs of Escherichia coli during designed manipulations of the rate of DNA replication identified aspects of both coupling elements. Enhanced frequencies of cell division were observed following an interval of reduced DNA replication rate, consistent with the prediction of a minimum possible distance between successive replisomes (an eclipse). As a corollary, the notion that cell poles are not always inert was confirmed by observed placement of division planes at perpendicular planes in monstrous and cuboidal cells containing multiple, segregating nucleoids.

Relationship between the function and the location of G1 cyclins inS. cerevisiae

2001 ◽  
Vol 114 (24) ◽  
pp. 4599-4611 ◽  
Author(s):  
Nicholas P. Edgington ◽  
Bruce Futcher
Keyword(s):  
Nuclear Localization ◽  
Cellular Localization ◽  
Subcellular Location ◽  
Nuclear Localization Sequence ◽  
Cyclin Dependent Kinase ◽  
Cyclin Dependent Kinases ◽  
G1 Cyclins ◽  
C Terminus ◽  
Localization Sequence ◽  
Nuclear Location

The Saccharomyces cerevisiae cyclin-dependent kinase Cdc28 forms complexes with nine different cyclins to promote cell division. These nine cyclin-Cdc28 complexes have different roles, but share the same catalytic subunit; thus, it is not clear how substrate specificity is achieved. One possible mechanism is specific sub-cellular localization of specific complexes. We investigated the location of two G1 cyclins using fractionation and microscopy. In addition, we developed ‘forced localization’ cassettes, which direct proteins to particular locations, to test the importance of localization. Cln2 was found in both nucleus and cytoplasm. A substrate of Cln2, Sic1, was also in both compartments. Cytoplasmic Cln2 was concentrated at sites of polarized growth. Forced localization showed that some functions of Cln2 required a cytoplasmic location, while other functions required a nuclear location. In addition, one function apparently required shuttling between the two compartments. The G1 cyclin Cln3 required nuclear localization. An autonomous, nuclear localization sequence was found near the C-terminus of Cln3. Our data supports the hypothesis that Cln2 and Cln3 have distinct functions and locations, and the specificity of cyclin-dependent kinases is mediated in part by subcellular location.

scholarly journals Plk is a functional homolog of Saccharomyces cerevisiae Cdc5, and elevated Plk activity induces multiple septation structures.

1997 ◽  
Vol 17 (6) ◽  
pp. 3408-3417 ◽  
Author(s):  
K S Lee ◽  
R L Erikson
Keyword(s):  
Saccharomyces Cerevisiae ◽  
Cell Cycle ◽  
Cell Division ◽  
Specific Activity ◽  
Ectopic Expression ◽  
Sf9 Cells ◽  
Wild Type ◽  
C Terminus ◽  
M Phase

Plk is a mammalian serine/threonine protein kinase whose activity peaks at the onset of M phase. It is closely related to other mammalian kinases, Snk, Fnk, and Prk, as well as to Xenopus laevis Plx1, Drosophila melanogaster polo, Schizosaccharomyces pombe Plo1, and Saccharomyces cerevisiae Cdc5. The M phase of the cell cycle is a highly coordinated process which insures the equipartition of genetic and cellular materials during cell division. To enable understanding of the function of Plk during M phase progression, various Plk mutants were generated and expressed in Sf9 cells and budding yeast. In vitro kinase assays with Plk immunoprecipitates prepared from Sf9 cells indicate that Glu206 and Thr210 play equally important roles for Plk activity and that replacement of Thr210 with a negatively charged residue elevates Plk specific activity. Ectopic expression of wild-type Plk (Plk WT) complements the cell division defect associated with the cdc5-1 mutation in S. cerevisiae. The degree of complementation correlates closely with the Plk activity measured in vitro, as it is enhanced by a mutationally activated Plk, T210D, but is not observed with the inactive forms K82M, D194N, and D194R. In a CDC5 wild-type background, expression of Plk WT or T210D, but not of inactive forms, induced a sharp accumulation of cells in G1. Consistent with elevated Plk activity, this phenomenon was enhanced by the C-terminally deleted forms WT deltaC and T210D deltaC. Expression of T210D also induced a class of cells with unusually elongated buds which developed multiple septal structures. This was not observed with the C-terminally deleted form T210D deltaC, however. It appears that the C terminus of Plk is not required for the observed cell cycle influence but may be important for polarized cell growth and septal structure formation.

Sign in / Sign up

Export Citation Format

Share Document