Generating asymmetry in a changing environment: cell cycle regulation in dimorphic alphaproteobacteria

2020 ◽  
Vol 401 (12) ◽  
pp. 1349-1363
Author(s):  
Muriel C. F. van Teeseling ◽  
Martin Thanbichler
Keyword(s):  
Cell Cycle ◽  
Dna Binding ◽  
Current Knowledge ◽  
Response Regulator ◽  
Binding Activity ◽  
Cell Fates ◽  
Cell Cycles ◽  
Dna Binding Activity ◽  
Distinct Cell ◽  
Cycle Regulation

AbstractWhile many bacteria divide by symmetric binary fission, some alphaproteobacteria have strikingly asymmetric cell cycles, producing offspring that differs significantly in their morphology and reproductive state. To establish this asymmetry, these species employ a complex cell cycle regulatory pathway based on two-component signaling cascades. At the center of this network is the essential DNA-binding response regulator CtrA, which acts as a transcription factor controlling numerous genes with cell cycle-relevant functions as well as a regulator of chromosome replication. The DNA-binding activity of CtrA is controlled at the level of both protein phosphorylation and stability, dependent on an intricate network of regulatory proteins, whose function is tightly coordinated in time and space. CtrA is differentially activated in the two (developing) offspring, thereby establishing distinct transcriptional programs that ultimately determine their distinct cell fates. Phase-separated polar microdomains of changing composition sequester proteins involved in the (in-)activation and degradation of CtrA specifically at each pole. In this review, we summarize the current knowledge of the CtrA pathway and discuss how it has evolved to regulate the cell cycle of morphologically distinct alphaproteobacteria.

scholarly journals Cell cycle-regulated transcription of the CLB2 gene is dependent on Mcm1 and a ternary complex factor.

1995 ◽  
Vol 15 (6) ◽  
pp. 3129-3137 ◽  
Author(s):  
M Maher ◽  
F Cong ◽  
D Kindelberger ◽  
K Nasmyth ◽  
S Dalton
Keyword(s):  
Cell Cycle ◽  
Dna Binding ◽  
Cell Cycle Regulation ◽  
Ternary Complex ◽  
Binding Activity ◽  
Transcriptional Level ◽  
Dna Binding Activity ◽  
Cycle Regulation ◽  
Ternary Complex Factor

Clb2 is the major B-type mitotic cyclin required for entry into mitosis in the budding yeast Saccharomyces cerevisiae. We showed that accumulation of CLB2 transcripts in G2 cells is controlled at the transcriptional level and identified a 55-bp upstream activating sequence (UAS) containing an Mcm1 binding site as being necessary and sufficient for cell cycle regulation. Sequences within the cell cycle-regulated UAS were shown to bind Mcm1 in vitro, and mutation which abolished Mcm1-dependent DNA binding activity eliminated cell cycle-regulated transcription in vivo. A second protein with no autonomous DNA binding activity was also recruited into Mcm1-UAS complexes, generating a ternary complex. A point mutation in the CLB2 UAS which blocked ternary complex formation, but still allowed Mcm1 to bind, resulted in loss of cell cycle regulation in vivo, suggesting that the ternary complex factor is also important in control of CLB2 transcription. We discuss the possibility that the CLB2 gene is coregulated with other genes known to be regulated with the same periodicity and suggest that Mcm1 and the ternary complex factor may coordinately regulate several other G2-regulated transcripts.

scholarly journals Cell Cycle Regulation of Nuclear Factor p92 DNA-binding Activity by Novel Phase-specific Inhibitors

1996 ◽  
Vol 271 (16) ◽  
pp. 9215-9222 ◽  
Author(s):  
Edgar Grinstein ◽  
Inge Weinert ◽  
Brigitte Droese ◽  
Michele Pagano ◽  
Hans-Dieter Royer
Keyword(s):  
Cell Cycle ◽  
Dna Binding ◽  
Cell Cycle Regulation ◽  
Binding Activity ◽  
Nuclear Factor ◽  
Dna Binding Activity ◽  
Cycle Regulation ◽  
Specific Inhibitors

scholarly journals Abundance Changes of the Response Regulator RcaC Require Specific Aspartate and Histidine Residues and Are Necessary for Normal Light Color Responsiveness

2008 ◽  
Vol 190 (21) ◽  
pp. 7241-7250 ◽  
Author(s):  
Lina Li ◽  
David M. Kehoe
Keyword(s):  
Dna Binding ◽  
Dynamic Range ◽  
Response Regulator ◽  
Red Light ◽  
Green Light ◽  
Binding Activity ◽  
Transcriptional Responses ◽  
Dna Binding Activity ◽  
Normal Light ◽  
Light Color

ABSTRACT RcaC is a large, complex response regulator that controls transcriptional responses to changes in ambient light color in the cyanobacterium Fremyella diplosiphon. The regulation of RcaC activity has been shown previously to require aspartate 51 and histidine 316, which appear to be phosphorylation sites that control the DNA binding activity of RcaC. All available data suggest that during growth in red light, RcaC is phosphorylated and has relatively high DNA binding activity, while during growth in green light RcaC is not phosphorylated and has less DNA binding activity. RcaC has also been found to be approximately sixfold more abundant in red light than in green light. Here we demonstrate that the light-controlled abundance changes of RcaC are necessary, but not sufficient, to direct normal light color responses. RcaC abundance changes are regulated at both the RNA and protein levels. The RcaC protein is significantly less stable in green light than in red light, suggesting that the abundance of this response regulator is controlled at least in part by light color-dependent proteolysis. We provide evidence that the regulation of RcaC abundance does not depend on any RcaC-controlled process but rather depends on the presence of the aspartate 51 and histidine 316 residues that have previously been shown to control the activity of this protein. We propose that the combination of RcaC abundance changes and modification of RcaC by phosphorylation may be necessary to provide the dynamic range required for transcriptional control of RcaC-regulated genes.

scholarly journals Cinnamaldehyde and cinnamaldehyde derivatives reduce virulence in Vibrio spp. by decreasing the DNA-binding activity of the quorum sensing response regulator LuxR

2008 ◽  
Vol 8 (1) ◽  
pp. 149 ◽  
Author(s):  
Gilles Brackman ◽  
Tom Defoirdt ◽  
Carol Miyamoto ◽  
Peter Bossier ◽  
Serge Van Calenbergh ◽  
...  
Keyword(s):  
Dna Binding ◽  
Quorum Sensing ◽  
Response Regulator ◽  
Binding Activity ◽  
Dna Binding Activity ◽  
Vibrio Spp

Evidence for DNA binding activity of numatrin (B23), a cell cycle-regulated nuclear matrix protein

1990 ◽  
Vol 1087 (2) ◽  
pp. 127-136 ◽  
Author(s):  
Nili Feuerstein ◽  
James J. Mond ◽  
Paul R. Kinchington ◽  
Robert Hickey ◽  
Marja-Liisa Karjalainen Lindsberg ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Dna Binding ◽  
Nuclear Matrix ◽  
Matrix Protein ◽  
Binding Activity ◽  
Nuclear Matrix Protein ◽  
Dna Binding Activity ◽  
A Cell

scholarly journals Constitutive c-Myb amino-terminal phosphorylation and DNA binding activity uncoupled during entry and passage through the cell cycle

Oncogene ◽  
2001 ◽  
Vol 20 (14) ◽  
pp. 1784-1792 ◽  
Author(s):  
Alina Cures ◽  
Colin House ◽  
Chie Kanei-Ishii ◽  
Bruce Kemp ◽  
Robert G Ramsay
Keyword(s):  
Cell Cycle ◽  
Dna Binding ◽  
Binding Activity ◽  
Amino Terminal ◽  
Dna Binding Activity

scholarly journals Phosphorylation Controls Ikaros's Ability To Negatively Regulate the G1-S Transition

2004 ◽  
Vol 24 (7) ◽  
pp. 2797-2807 ◽  
Author(s):  
Pablo Gómez-del Arco ◽  
Kazushige Maki ◽  
Katia Georgopoulos
Keyword(s):  
Cell Cycle ◽  
Dna Binding ◽  
Cell Cycle Progression ◽  
Rapid Development ◽  
Binding Activity ◽  
Casein Kinase ◽  
Cycle Progression ◽  
Dna Binding Activity ◽  
Increased Activity ◽  
Inactivating Mutations

ABSTRACT Ikaros is a key regulator of lymphocyte proliferative responses. Inactivating mutations in Ikaros cause antigen-mediated lymphocyte hyperproliferation and the rapid development of leukemia and lymphoma. Here we show that Ikaros's ability to negatively regulate the G1-S transition can be modulated by phosphorylation of a serine/threonine-rich conserved region (p1) in exon 8. Ikaros phosphorylation in p1 is induced during the G1-S transition. Mutations that prevent phosphorylation in p1 increase Ikaros's ability to impede cell cycle progression and its affinity for DNA. Casein kinase II, whose increased activity in lymphocytes leads to transformation, is a key player in Ikaros p1 phosphorylation. We thus propose that Ikaros's activity as a regulator of the G1-S transition is controlled by phosphorylation in response to signaling events that downmodulate its DNA binding activity.

Imatinib Induced Re-Activation of FoxO3 Transcription Factor in CML Is Responsible for the Induction of a Quiescent Status of CD34 Leukaemic Progenitor Cells.

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 1090-1090
Author(s):  
Daniela Cilloni ◽  
Cristina Panuzzo ◽  
Francesca Messa ◽  
Francesca Arruga ◽  
Enrico Bracco ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Cell Growth ◽  
Dna Binding ◽  
Progenitor Cells ◽  
Binding Activity ◽  
Mrna Levels ◽  
Dna Binding Activity ◽  
Cd34 Cells

Abstract The FoxO family of transcription factors is regulated by PI3K/Akt induced phosphorylation resulting in nuclear exclusion and degradation. Nuclear FoxO transcribes proapoptotic molecules and cell cycle inhibitors. In CML cells the TK activity of Bcr-Abl leads to the abnormal activation of downstream effectors including PI3K/Akt. The aim of this study was to investigate the role of FoxO3 in Bcr-Abl induced apoptotic arrest and cell growth and the effect of imatinib (IM) induced re-activation of FoxO3 activity in CML progenitor cells. BM cells were collected from 52 CML patients and 20 healthy donors. The expression level of FoxO3 was tested by RQ-PCR. The protein amount and localization was analyzed by Western blot and immunofluorescence, DNA binding activity was measured by EMSA. In addition, FoxO3 was analyzed in CML primary cells and CD34+ cells after IM incubation. Cell cycle and the expression levels of CD47, which has been demonstrated to increased during progression through the cell cycle and stem cell mobilization, was measured by FACS in CD34+ cell population. In addition K562 cells was transfected with pECE-FoxO3 to clarify FoxO3 effects on cell growth and apoptosis. Finally we used our already set up model of Drosophila melanogaster (Dm) transgenic for human Bcr-Abl to study the pathway leading to FoxO3 inactivation. We found that, despite either FoxO3 mRNA levels or protein amount are similar in CML cells compared to controls, FoxO3 protein is equally distributed in the nucleus and cytoplasm in controls but it is completely cytoplasmatic in CML cells and it enters the nucleus during in vivo IM treatment or in vitro IM incubation. Additionally, FoxO3 DNA binding activity in CML patients is completely absent at diagnosis and reappears after IM treatment. Moreover FoxO3 overexpression in transfected cells results into a 49±9 % reduction of proliferation which was further reduced of 75±5 % after IM incubation. Furthermore, we demonstrated that IM incubation results into the reactivation of FoxO3 in Ph+ CD34+ cells inducing quiescence into this population as demonstrated by the comparison of cell cycle kinetics and by a decreased expression of CD47. Finally, the progeny obtained from the crossbreeding of Bcr-Abl flies and flies transgenic for FoxO showed a rescue of FoxO phenotype demonstrating that FoxO inactivation is Bcr-Abl mediated. Overall, these in vitro and in vivo experiments suggest that FoxO3 is inactivated in CML cells and its delocalization is mainly dependant from Bcr-Abl activity. The antiproliferative activity of IM may be mediated by FoxO3 re-localization. On the other side, FoxO3 re-activation induced by IM results into a quiescence of Bcr-Abl CD34+ progenitor cells, which raises a hypothesis that FoxO3 could play a role in IM resistance. This investigation was conducted by CML Correlative Studies Network (CCSN), TOPS, which is sponsored by Novartis Oncology

scholarly journals The DNA Binding Activity of C/EBP Transcription Factors Is Regulated in the G Phase of the Hepatocyte Cell Cycle

1995 ◽  
Vol 270 (30) ◽  
pp. 18123-18132 ◽  
Author(s):  
Basabi Rana ◽  
Yuhong Xie ◽  
David Mischoulon ◽  
Nancy L. R. Bucher ◽  
Stephen R. Farmer
Keyword(s):  
Cell Cycle ◽  
Transcription Factors ◽  
Dna Binding ◽  
Binding Activity ◽  
Dna Binding Activity

scholarly journals M-phase-specific phosphorylation of the POU transcription factor GHF-1 by a cell cycle-regulated protein kinase inhibits DNA binding.

1995 ◽  
Vol 15 (12) ◽  
pp. 6694-6701 ◽  
Author(s):  
C Caelles ◽  
H Hennemann ◽  
M Karin
Keyword(s):  
Cell Cycle ◽  
Transcription Factor ◽  
Protein Kinase ◽  
Dna Binding ◽  
Binding Activity ◽  
Dependent Manner ◽  
Mitotic Kinase ◽  
Dna Binding Activity ◽  
M Phase ◽  
A Cell

GHF-1 is a member of the POU family of homeodomain proteins. It is a cell-type-specific transcription factor responsible for determination and expansion of growth hormone (GH)- and prolactin-expressing cells in the anterior pituitary. It was previously suggested that cyclic AMP (cAMP)-responsive protein kinase A (PKA) phosphorylates GHF-1 at a site within the N-terminal arm of its homeodomain, thereby inhibiting its binding to the GH promoter. These results, however, are inconsistent with the physiological stimulation of GH production by the cAMP pathway. As reported here, cAMP agonists and PKA do not inhibit GHF-1 activity in living cells and although they stimulate the phosphorylation of GHF-1, the inhibitory phosphoacceptor site within the homeodomain is not affected. Instead, this site, Thr-220, is subject to M-phase-specific phosphorylation. As a result, GHF-1 DNA binding activity is transiently inhibited during the M phase. This activity is regained once cells enter G1, a phase during which GHF-1 phosphorylation is minimal. Thr-220 of GHF-1 is the homolog of the mitotic phosphoacceptor site responsible for the M-phase-specific inhibition of Oct-1 DNA binding Ser-382. As this site is conserved in all POU proteins, it appears that all members of this group are similarly regulated. A specific kinase activity distinct in its substrate specificity and susceptibility to inhibitors from the Cdc2 mitotic kinase or PKA was identified in extracts of mitotic cells. This novel activity could be involved in regulating the DNA binding activity of all POU proteins in a cell cycle-dependent manner.

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