scholarly journals Cell cycle-dependent phosphorylation and regulation of cellular differentiation

2018 ◽  
Vol 46 (5) ◽  
pp. 1083-1091 ◽  
Author(s):  
Laura J.A. Hardwick ◽  
Roberta Azzarelli ◽  
Anna Philpott

Embryogenesis requires an exquisite regulation of cell proliferation, cell cycle withdrawal and differentiation into a massively diverse range of cells at the correct time and place. Stem cells also remain to varying extents in different adult tissues, acting in tissue homeostasis and repair. Therefore, regulated proliferation and subsequent differentiation of stem and progenitor cells remains pivotal throughout life. Recent advances have characterised the cell cycle dynamics, epigenetics, transcriptome and proteome accompanying the transition from proliferation to differentiation, revealing multiple bidirectional interactions between the cell cycle machinery and factors driving differentiation. Here, we focus on a direct mechanistic link involving phosphorylation of differentiation-associated transcription factors by cell cycle-associated Cyclin-dependent kinases. We discuss examples from the three embryonic germ layers to illustrate this regulatory mechanism that co-ordinates the balance between cell proliferation and differentiation.

2014 ◽  
Vol 42 (5) ◽  
pp. 1471-1476 ◽  
Author(s):  
Alessandro Poli ◽  
Sara Mongiorgi ◽  
Lucio Cocco ◽  
Matilde Y. Follo

Protein kinases C (PKCs) are a family of serine/threonine kinases which act as key regulators in cell cycle progression and differentiation. Studies of the involvement of PKCs in cell proliferation showed that their role is dependent on cell models, cell cycle phases, timing of activation and localization. Indeed, PKCs can positively and negatively act on it, regulating entry, progression and exit from the cell cycle. In particular, the targets of PKCs resulted to be some of the key proteins involved in the cell cycle including cyclins, cyclin-dependent kinases (Cdks), Cip/Kip inhibitors and lamins. Several findings described roles for PKCs in the regulation of G1/S and G2/M checkpoints. As a matter of fact, data from independent laboratories demonstrated PKC-related modulations of cyclins D, leading to effects on the G1/S transition and differentiation of different cell lines. Moreover, interesting data were published on PKC-mediated phosphorylation of lamins. In addition, PKC isoenzymes can accumulate in the nuclei, attracted by different stimuli including diacylglycerol (DAG) fluctuations during cell cycle progression, and target lamins, leading to their disassembly at mitosis. In the present paper, we briefly review how PKCs could regulate cell proliferation and differentiation affecting different molecules related to cell cycle progression.


2010 ◽  
Vol 107 (5) ◽  
pp. 1876-1881 ◽  
Author(s):  
Chunnian Zhao ◽  
GuoQiang Sun ◽  
Shengxiu Li ◽  
Ming-Fei Lang ◽  
Su Yang ◽  
...  

Neural stem cell self-renewal and differentiation is orchestrated by precise control of gene expression involving nuclear receptor TLX. Let-7b, a member of the let-7 microRNA family, is expressed in mammalian brains and exhibits increased expression during neural differentiation. However, the role of let-7b in neural stem cell proliferation and differentiation remains unknown. Here we show that let-7b regulates neural stem cell proliferation and differentiation by targeting the stem cell regulator TLX and the cell cycle regulator cyclin D1. Overexpression of let-7b led to reduced neural stem cell proliferation and increased neural differentiation, whereas antisense knockdown of let-7b resulted in enhanced proliferation of neural stem cells. Moreover, in utero electroporation of let-7b to embryonic mouse brains led to reduced cell cycle progression in neural stem cells. Introducing an expression vector of Tlx or cyclin D1 that lacks the let-7b recognition site rescued let-7b-induced proliferation deficiency, suggesting that both TLX and cyclin D1 are important targets for let-7b-mediated regulation of neural stem cell proliferation. Let-7b, by targeting TLX and cyclin D1, establishes an efficient strategy to control neural stem cell proliferation and differentiation.


2015 ◽  
Vol 59 (4) ◽  
Author(s):  
F. Aredia ◽  
M. Malatesta ◽  
P. Veneroni ◽  
M.G. Bottone

<p>Extracellular signal-regulated kinases (ERK) 1, 2 and 3 are involved in cell proliferation and differentiation, and apoptosis; although ERK1/2 have been widely studied, limited knowledge on ERK3 is available. The present work aimed at investigating ERK3 distribution during cell cycle and apoptosis in human tumor HeLa cells. The analysis performed by double immunofluorescence and immunoelectron microscopy experiments revealed that during interphase ERK3 is mainly resident in the nucleoplasm in association with ribonuclear proteins involved in early pre-mRNA splicing, it undergoes cell cycle-dependent redistribution and, during apoptosis, it remains in the nucleus in the form of massive nuclear aggregates, then moves to the cytoplasm and is finally extruded.</p>


PPAR Research ◽  
2007 ◽  
Vol 2007 ◽  
pp. 1-10 ◽  
Author(s):  
A. Cimini ◽  
L. Cristiano ◽  
E. Benedetti ◽  
B. D'Angelo ◽  
M. P. Cerù

PPAR isotypes are involved in the regulation of cell proliferation, death, and differentiation, with different roles and mechanisms depending on the specific isotype and ligand and on the differentiated, undifferentiated, or transformed status of the cell. Differentiation stimuli are integrated by key transcription factors which regulate specific sets of specialized genes to allow proliferative cells to exit the cell cycle and acquire specialized functions. The main differentiation programs known to be controlled by PPARs both during development and in the adult are placental differentiation, adipogenesis, osteoblast differentiation, skin differentiation, and gut differentiation. PPARs may also be involved in the differentiation of macrophages, brain, and breast. However, their functions in this cell type and organs still awaits further elucidation. PPARs may be involved in cell proliferation and differentiation processes of neural stem cells (NSC). To this aim, in this work the expression of the three PPAR isotypes and RXRs in NSC has been investigated.


1992 ◽  
Vol 40 (5) ◽  
pp. 619-627 ◽  
Author(s):  
G A Hyatt ◽  
D C Beebe

We developed a double-label method to directly measure the rate at which cells enter S-phase of the cell cycle. All cells in S-phase were first labeled with a short pulse of [3H]-thymidine. This was followed by a longer incubation in bromodeoxyuridine (BrdU), a thymidine analogue. Nuclei labeled with [3H]-thymidine were detected by autoradiography and those labeled with BrdU by immunocytochemistry. Cells labeled only with BrdU must have entered S-phase at some time after the end of the [3H]-thymidine pulse. Thus, the rate of entry of cells into S-phase could be determined. This method was shown to be more accurate and more sensitive than determining changes in the rate at which cells entered S-phase with a continuous labeling protocol. It was possible to detect changes in proliferative activity that occurred in less than 1 hr. We used this double-label technique to study changes in the cell cycle during the terminal differentiation of chicken embryo lens fiber cells. These studies revealed differences in the effects of several treatments known to stimulate fiber cell differentiation. They also demonstrated the presence in the embryonic eye of factors that stimulate and prevent lens cell proliferation and differentiation.


2020 ◽  
Vol 21 (14) ◽  
pp. 4925
Author(s):  
Estephania Zluhan-Martínez ◽  
Vadim Pérez-Koldenkova ◽  
Martha Verónica Ponce-Castañeda ◽  
María de la Paz Sánchez ◽  
Berenice García-Ponce ◽  
...  

The Retinoblastoma protein (pRb) is a key cell cycle regulator conserved in a wide variety of organisms. Experimental analysis of pRb’s functions in animals and plants has revealed that this protein participates in cell proliferation and differentiation processes. In addition, pRb in animals and its orthologs in plants (RBR), are part of highly conserved protein complexes which suggest the possibility that analogies exist not only between functions carried out by pRb orthologs themselves, but also in the structure and roles of the protein networks where these proteins are involved. Here, we present examples of pRb/RBR participation in cell cycle control, cell differentiation, and in the regulation of epigenetic changes and chromatin remodeling machinery, highlighting the similarities that exist between the composition of such networks in plants and animals.


1972 ◽  
Vol 52 (1) ◽  
pp. 161-175 ◽  
Author(s):  
N. A. WRIGHT ◽  
A. R. MORLEY ◽  
D. APPLETON

SUMMARY The action of testosterone on the cell kinetics of the small bowel was studied in the castrated male mouse. The parameters of the cell cycle were measured using the labelled mitoses method. No difference was found between cell cycle parameters in testosterone-treated castrated animals compared with castrated controls. Crypt cell kinetics were studied by measuring the distribution of labelled and mitotic nuclei using a computer programme. The labelling and mitotic indices were significantly raised in the testosterone-treated animals. There was also a significant upward displacement of the cut-off position in the testosterone-treated group, indicating an increase in the size of the proliferative compartment, and thus an increase in growth fraction. This change in growth fraction was confirmed by calculation from the labelled mitoses results, and is considered to be the mechanism by which testosterone stimulates cell proliferation in the small bowel of the castrated mouse. The action of testosterone on the growth fraction may constitute an important component of the general mitogenic effect of the hormone on both target and non-target tissues.


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