scholarly journals Deceleration of cell cycle underpins a switch from proliferative- to terminal division in plant stomatal lineage

2021 ◽  
Author(s):  
Soon-Ki Han ◽  
Jiyuan Yang ◽  
Machiko Arakawa ◽  
Rie Iwasaki ◽  
Tomoaki Sakamoto ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Kinase Inhibitor ◽  
Cell Cycle Control ◽  
Control Plant ◽  
Time Lapse ◽  
Cell Types ◽  
Symmetric Division ◽  
Cyclin Dependent Kinase Inhibitor ◽  
Asymmetric Divisions ◽  
Stomatal Lineage

Differentiation of specialized cell types from self-renewing progenitors requires precise cell cycle control. Plant stomata are generated through asymmetric divisions of a stem-cell-like precursor meristemoid followed by the single symmetric division that creates an adjustable pore surrounded by paired guard cells. The stomatal-lineage-specific transcription factor MUTE terminates the asymmetric divisions and triggers differentiation. However, the role of cell cycle machinery in this transition remains unknown. Through time-lapse imaging, we discover that the symmetric division is slower than the asymmetric division. We identify a plant-specific cyclin-dependent kinase inhibitor, SIAMESE-RELATED4 (SMR4), as a molecular brake that decelerates cell cycle during this transition. SMR4 is directly induced by MUTE and transiently accumulates in differentiating meristemoids. SMR4 physically and functionally associates with CYCD3;1 and extends G1-phase of asymmetric divisions. By contrast, SMR4 fails to interact with CYCD5;1, a MUTE-induced G1 cyclin, and permits the symmetric division. Our work unravels a molecular framework of the proliferation-to-differentiation switch within the stomatal lineage and suggests that a timely proliferative cell cycle is critical for the stomatal fate specification.

scholarly journals Differential activation of target cellular promoters by p53 mutants with impaired apoptotic function.

1996 ◽  
Vol 16 (9) ◽  
pp. 4952-4960 ◽  
Author(s):  
R L Ludwig ◽  
S Bates ◽  
K H Vousden
Keyword(s):  
Cell Cycle ◽  
Cell Cycle Arrest ◽  
Dna Sequences ◽  
Transcriptional Activation ◽  
Cellular Response ◽  
Kinase Inhibitor ◽  
Cell Types ◽  
Cyclin Dependent Kinase Inhibitor ◽  
Cycle Arrest ◽  
P53 Tumor Suppressor Protein

The p53 tumor suppressor protein is a sequence-specific transcriptional activator, a function which contributes to cell cycle arrest and apoptosis induced by p53 in appropriate cell types. Analysis of a series of p53 point mutants has revealed the potential for selective loss of the ability to transactivate some, but not all, cellular p53-responsive promoters. p53 175P and p53 181L are tumor-derived p53 point mutants which were previously characterized as transcriptionally active. Both mutants retained the ability to activate expression of the cyclin-dependent kinase inhibitor p2lcip1/waf1, and this activity correlated with the ability to induce a G1 cell cycle arrest. However, an extension of this survey to include other p53 targets showed that p53 175P was defective in the activation of p53-responsive sequences derived from the bax promoter and the insulin-like growth factor-binding protein 3 gene (IGF-BP3) promoter, while p53 181L showed loss of the ability to activate a promoter containing IGF-BP3 box B sequences. Failure to activate transcription was also reflected in the reduced ability of the mutants to bind the p53-responsive DNA sequences present in these promoters. These specific defects in transcriptional activation correlated with the impaired apoptotic function displayed by these mutants, and the results suggest that activation of cell cycle arrest genes by p53 can be separated from activation of genes with a role in mediating the p53 apoptotic response. The cellular response to p53 activation may therefore depend, at least in part, on which group of p53-responsive genes become transcriptionally activated.

scholarly journals Control of multiciliogenesis by miR-34/449 in the male reproductive tract through enforcing cell cycle exit

2021 ◽  
Author(s):  
Yu-Jie Wu ◽  
Yue Liu ◽  
Yan-Qin Hu ◽  
Li Wang ◽  
Fu-Rong Bai ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Reproductive Tract ◽  
Surface Defects ◽  
Kinase Inhibitor ◽  
Cell Cycle Control ◽  
Apical Surface ◽  
Cell Cycle Exit ◽  
Double Knockout ◽  
Cyclin Dependent Kinase Inhibitor ◽  
Cilia Formation

Multiciliated cells (MCCs) are terminally differentiated, post-mitotic cells that possess hundreds of motile cilia on their apical surface. Defects in cilia formation are associated with ciliopathies that affect many organs. In the present study, we tested the role and mechanism of the miR-34/449 family in the regulation of multiciliogenesis in efferent ductules (EDs) using a miR-34b/c−/-; miR-449−/- double knockout (dKO) mouse model. MiR-34b/c and miR-449 depletion led to a reduced number of MCCs and abnormal cilia structure in the EDs starting from postnatal day 14. However, abnormal MCC differentiation in the dKO EDs could be observed as early as postnatal day 7. RNA-seq analyses revealed that the aberrant development of MCCs in the EDs of dKO mice was associated with upregulation of genes involved in cell cycle control. Using a cyclin dependent kinase inhibitor to force cell cycle exit promoted MCC differentiation, and partially rescued the defective multiciliogenesis in the EDs of dKO mice. Taken together, our results suggested that miR-34b/c and miR-449 play an essential role in multiciliogenesis in EDs by regulating cell cycle exit.

Human lactoferrin controls the level of retinoblastoma protein and its activityThis paper is one of a selection of papers published in this Special Issue, entitled 7th International Conference on Lactoferrin: Structure, Function, and Applications, and has undergone the Journal's usual peer review process.

2006 ◽  
Vol 84 (3) ◽  
pp. 345-350 ◽  
Author(s):  
Hee-Joung Son ◽  
Shin-Hee Lee ◽  
Sang-Yun Choi
Keyword(s):  
Cell Cycle ◽  
Cell Growth ◽  
Kinase Inhibitor ◽  
Peer Review Process ◽  
Cell Cycle Control ◽  
Retinoblastoma Protein ◽  
Cyclin Dependent Kinase ◽  
Antiproliferative Effects ◽  
Cyclin Dependent Kinase Inhibitor ◽  
Selection Of

Lactoferrin (Lf) has been implicated in the regulation of cell growth. However, the molecular mechanism underlying this effect remains to be elucidated. In this study, we show that Lf is involved in the cell cycle control system in a variety of cell lines, through retinoblastoma protein (Rb) - mediated growth arrest. We observed that Lf induces the expression of Rb, a signal mediator of cell cycle control, and that a majority of this Lf-induced Rb persists in a hypophosphorylated form. In addition, we determined that Lf specifically augments the level of a cyclin-dependent kinase inhibitor, p21, but not p27. Upon treatment with Lf, H1299 cells expressing defective p53 effected an augmentation of endogenous p21 levels, which may contribute to the accumulation of hypophosphorylated Rb. A substantial quantity of active Rb binds more efficiently to E2F1 in cells that express Lf and consequently blocks the expression of an E2F1-responsive gene, thereby suggesting that Lf plays a crucial role in the inhibition of tumor cell growth. Therefore, we conclude that the antiproliferative effects of Lf can likely be attributed to the elevated levels of hypophosphorylated Rb.

scholarly journals Cyclin D2 Translocates p27 out of the Nucleus and Promotes Its Degradation at the G0-G1 Transition

2007 ◽  
Vol 27 (13) ◽  
pp. 4626-4640 ◽  
Author(s):  
Etsuo Susaki ◽  
Keiko Nakayama ◽  
Keiichi I. Nakayama
Keyword(s):  
Cell Cycle ◽  
Rna Interference ◽  
Nuclear Export ◽  
Kinase Inhibitor ◽  
Cell Types ◽  
Cyclin Dependent Kinase ◽  
Cyclin D2 ◽  
Mitogenic Stimulation ◽  
Cyclin Dependent Kinase Inhibitor ◽  
The Stability

ABSTRACT The nuclear export and cytoplasmic degradation of the cyclin-dependent kinase inhibitor p27 are required for effective progression of the cell cycle through the G0-G1 transition. The mechanism responsible for this translocation of p27 has remained unclear, however. We now show that cyclin D2 directly links growth signaling with the nuclear export of p27 at the G0-G1 transition in some cell types. The up-regulation of cyclin D2 in response to mitogenic stimulation was found to occur earlier than that of other D-type cyclins and in parallel with down-regulation of p27 at the G0-G1 transition. RNA interference-mediated depletion of cyclin D2 inhibited the nuclear export of p27 and delayed its degradation at the G0-G1 transition. In contrast, overexpression of cyclin D2 in G0 phase shifted the localization of p27 from the nucleus to the cytoplasm and reduced the stability of p27. Overexpression of the cyclin D2(T280A) mutant, whose export from the nucleus is impaired, prevented the translocation and degradation of p27. These results indicate that cyclin D2 translocates p27 from the nucleus into the cytoplasm for its KPC-dependent degradation at the G0-G1 transition.

scholarly journals Growth Inhibition by the Tumor Suppressor p33ING1 in Immortalized and Primary Cells: Involvement of Two Silencing Domains and Effect of Ras

2005 ◽  
Vol 25 (1) ◽  
pp. 422-431 ◽  
Author(s):  
Frauke Goeman ◽  
Dorit Thormeyer ◽  
Maria Abad ◽  
Manuel Serrano ◽  
Oliver Schmidt ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Tumor Suppressor ◽  
Kinase Inhibitor ◽  
Trichostatin A ◽  
Cell Cycle Control ◽  
Human Fibroblasts ◽  
Cell Types ◽  
Histone Deacetylation ◽  
Dominant Negative ◽  
Mitogen Activated Protein Kinase

ABSTRACT ING1 was identified as an inhibitor of growth and has been described as a tumor suppressor. Furthermore, the expression of ING1 is induced in senescent cells and antisense ING1 extends the proliferative life span of primary human fibroblasts. Cooperation of p33ING1 with p53 has been suggested to be an important function of ING1 in cell cycle control. Intriguingly, it has been shown that p33ING1 is associated with histone acetylation as well as with histone deacetylation function. Here we show that p33ING1 is a potent transcriptional silencer in various cell types. However, the silencing function is independent of the presence of p53. By use of deletion mutants two potent autonomous and transferable silencing domains were identified, but no evidence of an activation domain was found. The amino (N)-terminal silencing domain is sensitive to the histone deacetylase inhibitor trichostatin A (TSA) whereas the carboxy-terminal silencing function is resistant to TSA, suggesting that p33ING1 confers gene silencing through both HDAC-dependent and -independent mechanisms. Interestingly, the presence of oncogenic Ras, which is able to induce premature senescence, increases the p33ING1-mediated silencing function. Moreover, ING1-mediated silencing was reduced by coexpressing dominant-negative Ras or by treatment with the mitogen-activated protein kinase inhibitor PD98059 but not by treatment with SB203580, an inhibitor of the p38 pathway. In addition, we show that both silencing domains of ING1 are involved in cell cycle control, as measured by inhibition of colony formation of immortalized cells and by thymidine incorporation of primary human diploid fibroblasts (HDF). Interestingly, p33ING1 expression induces features of cellular senescence in HDFs.

scholarly journals E2F4 Is Exported from the Nucleus in a CRM1-Dependent Manner

2001 ◽  
Vol 21 (4) ◽  
pp. 1384-1392 ◽  
Author(s):  
Stefan Gaubatz ◽  
Jacqueline A. Lees ◽  
Geoffrey J. Lindeman ◽  
David M. Livingston
Keyword(s):  
Cell Cycle ◽  
Cell Cycle Arrest ◽  
Nuclear Export ◽  
Kinase Inhibitor ◽  
Cell Cycle Control ◽  
Specific Inhibitor ◽  
Cell Types ◽  
Dependent Manner ◽  
Cycle Arrest ◽  
Nuclear Export Receptor

ABSTRACT E2F is a family of transcription factors required for normal cell cycle control and for cell cycle arrest in G1. E2F4 is the most abundant E2F protein in many cell types. In quiescent cells, it is localized to the nucleus, where it is bound to the retinoblastoma-related protein p130. During entry into the cell cycle, the protein disappears from the nucleus and appears in the cytoplasm. The mechanism by which this change occurs has, in the past, been unclear. We have found that E2F4 is actively exported from the nucleus and that leptomycin B, a specific inhibitor of nuclear export, inhibits this process. E2F4 export is mediated by two hydrophobic export sequences, mutations in either of which result in export failure. Individual export mutants of E2F4, but not a mutant with inactivation of both export signals, can be efficiently excluded from the nucleus by forced coexpression of the nuclear export receptor CRM1. Similarly, CRM1 overexpression can prevent cell cycle arrest induced by the cyclin kinase inhibitor p16INK4a, an E2F4-dependent process. Taken together, these data suggest that nuclear export contributes to the regulation of E2F4 function, including its ability to regulate exit from G1 in association with a suitable pocket protein.

scholarly journals Characterization of the p53-Dependent Postmitotic Checkpoint following Spindle Disruption

1998 ◽  
Vol 18 (2) ◽  
pp. 1055-1064 ◽  
Author(s):  
Jennifer S. Lanni ◽  
Tyler Jacks
Keyword(s):  
Cell Cycle ◽  
Dna Damage ◽  
Kinase Inhibitor ◽  
Time Window ◽  
Critical Role ◽  
Time Lapse ◽  
Suppressor Gene ◽  
Cell Cycle Checkpoint ◽  
Cyclin Dependent Kinase Inhibitor ◽  
Cycle Checkpoint

ABSTRACT The p53 tumor suppressor gene product is known to act as part of a cell cycle checkpoint in G1 following DNA damage. In order to investigate a proposed novel role for p53 as a checkpoint at mitosis following disruption of the mitotic spindle, we have used time-lapse videomicroscopy to show that both p53+/+ and p53−/− murine fibroblasts treated with the spindle drug nocodazole undergo transient arrest at mitosis for the same length of time. Thus, p53 does not participate in checkpoint function at mitosis. However, p53 does play a critical role in nocodazole-treated cells which have exited mitotic arrest without undergoing cytokinesis and have thereby adapted. We have determined that in nocodazole-treated, adapted cells, p53 is required during a specific time window to prevent cells from reentering the cell cycle and initiating another round of DNA synthesis. Despite having 4N DNA content, adapted cells are similar to G1 cells in that they have upregulated cyclin E expression and hypophosphorylated Rb protein. The mechanism of the p53-dependent arrest in nocodazole-treated adapted cells requires the cyclin-dependent kinase inhibitor p21, as p21−/−fibroblasts fail to arrest in response to nocodazole treatment and become polyploid. Moreover, p21 is required to a similar extent to maintain cell cycle arrest after either nocodazole treatment or irradiation. Thus, the p53-dependent checkpoint following spindle disruption functionally overlaps with the p53-dependent checkpoint following DNA damage.

Sign in / Sign up

Export Citation Format

Share Document