scholarly journals Bromodomain Protein Brd4 Binds to GTPase-Activating SPA-1, Modulating Its Activity and Subcellular Localization

2004 ◽  
Vol 24 (20) ◽  
pp. 9059-9069 ◽  
Author(s):  
Andrea Farina ◽  
Masakazu Hattori ◽  
Jun Qin ◽  
Yoshihiro Nakatani ◽  
Nagahiro Minato ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Subcellular Localization ◽  
Cell Cycle Progression ◽  
Ectopic Expression ◽  
Gtpase Activating Protein ◽  
Functional Importance ◽  
Cycle Progression ◽  
Proper Balance ◽  
Mammalian Protein ◽  
Normal Cell Cycle

ABSTRACT Brd4 is a mammalian protein that contains a double bromodomain. It binds to chromatin and regulates cell cycle progression at multiple stages. By immunopurification and mass spectrometry, we identified a Rap GTPase-activating protein (GAP), signal-induced proliferation-associated protein 1 (SPA-1), as a factor that interacts with Brd4. SPA-1 localizes to the cytoplasm and to a lesser degree in the nucleus, while Brd4 resides in the nucleus. Bifluorescence complementation revealed that Brd4 and SPA-1 interact with each other in the nucleus of living cells. Supporting the functional importance of the interaction, Brd4 enhanced Rap GAP activity of SPA-1. Furthermore ectopic expression of SPA-1 and Brd4 redirected subcellular localization of the partner and disrupted normal cell cycle progression. These effects were, however, reversed by coexpression of the two proteins, indicating that a proper balance between Brd4 and SPA-1 in G2 is required for cell division. This work reveals a novel link between Brd4 and a GTPase-dependent mitogenic signaling pathway.

Cyclin specificity: how many wheels do you need on a unicycle?

2001 ◽  
Vol 114 (10) ◽  
pp. 1811-1820 ◽  
Author(s):  
M.E. Miller ◽  
F.R. Cross
Keyword(s):  
Cell Cycle ◽  
Subcellular Localization ◽  
Cell Cycle Progression ◽  
Eukaryotic Cell ◽  
Cyclin Dependent Kinase ◽  
Temporal Expression ◽  
Cycle Progression

Cyclin-dependent kinase (CDK) activity is essential for eukaryotic cell cycle events. Multiple cyclins activate CDKs in all eukaryotes, but it is unclear whether multiple cyclins are really required for cell cycle progression. It has been argued that cyclins may predominantly act as simple enzymatic activators of CDKs; in opposition to this idea, it has been argued that cyclins might target the activated CDK to particular substrates or inhibitors. Such targeting might occur through a combination of factors, including temporal expression, protein associations, and subcellular localization.

scholarly journals Chk1-mediated Cdc25A degradation as a critical mechanism for normal cell cycle progression

2019 ◽  
Vol 132 (2) ◽  
pp. jcs223123 ◽  
Author(s):  
Hidemasa Goto ◽  
Toyoaki Natsume ◽  
Masato T. Kanemaki ◽  
Aika Kaito ◽  
Shujie Wang ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Normal Cell ◽  
Cell Cycle Progression ◽  
Cycle Progression ◽  
Normal Cell Cycle

scholarly journals The decision to enter mitosis: feedback and redundancy in the mitotic entry network

2009 ◽  
Vol 185 (2) ◽  
pp. 193-202 ◽  
Author(s):  
Arne Lindqvist ◽  
Verónica Rodríguez-Bravo ◽  
René H. Medema
Keyword(s):  
Cell Cycle ◽  
Normal Cell ◽  
Cell Cycle Progression ◽  
Feedback Loops ◽  
Cyclin B ◽  
Cycle Progression ◽  
Mitotic Entry ◽  
Different Levels ◽  
Normal Cell Cycle

The decision to enter mitosis is mediated by a network of proteins that regulate activation of the cyclin B–Cdk1 complex. Within this network, several positive feedback loops can amplify cyclin B–Cdk1 activation to ensure complete commitment to a mitotic state once the decision to enter mitosis has been made. However, evidence is accumulating that several components of the feedback loops are redundant for cyclin B–Cdk1 activation during normal cell division. Nonetheless, defined feedback loops become essential to promote mitotic entry when normal cell cycle progression is perturbed. Recent data has demonstrated that at least three Plk1-dependent feedback loops exist that enhance cyclin B–Cdk1 activation at different levels. In this review, we discuss the role of various feedback loops that regulate cyclin B–Cdk1 activation under different conditions, the timing of their activation, and the possible identity of the elusive trigger that controls mitotic entry in human cells.

scholarly journals A novel form of Deleted in breast cancer 1 (DBC1) lacking the N-terminal domain does not bind SIRT1 and is dynamically regulated in vivo

2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Leonardo Santos ◽  
Laura Colman ◽  
Paola Contreras ◽  
Claudia C. Chini ◽  
Adriana Carlomagno ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cell Cycle ◽  
Liver Regeneration ◽  
Partial Hepatectomy ◽  
Normal Cell ◽  
Cell Cycle Progression ◽  
Cycle Progression ◽  
Quiescent Cells ◽  
Normal Cell Cycle

Abstract The protein Deleted in Breast Cancer-1 is a regulator of several transcription factors and epigenetic regulators, including HDAC3, Rev-erb-alpha, PARP1 and SIRT1. It is well known that DBC1 regulates its targets, including SIRT1, by protein-protein interaction. However, little is known about how DBC1 biological activity is regulated. In this work, we show that in quiescent cells DBC1 is proteolytically cleaved, producing a protein (DN-DBC1) that misses the S1-like domain and no longer binds to SIRT1. DN-DBC1 is also found in vivo in mouse and human tissues. Interestingly, DN-DBC1 is cleared once quiescent cells re-enter to the cell cycle. Using a model of liver regeneration after partial hepatectomy, we found that DN-DBC1 is down-regulated in vivo during regeneration. In fact, WT mice show a decrease in SIRT1 activity during liver regeneration, coincidentally with DN-DBC1 downregulation and the appearance of full length DBC1. This effect on SIRT1 activity was not observed in DBC1 KO mice. Finally, we found that DBC1 KO mice have altered cell cycle progression and liver regeneration after partial hepatectomy, suggesting that DBC1/DN-DBC1 transitions play a role in normal cell cycle progression in vivo after cells leave quiescence. We propose that quiescent cells express DN-DBC1, which either replaces or coexist with the full-length protein, and that restoring of DBC1 is required for normal cell cycle progression in vitro and in vivo. Our results describe for the first time in vivo a naturally occurring form of DBC1, which does not bind SIRT1 and is dynamically regulated, thus contributing to redefine the knowledge about its function.

scholarly journals Dynamic regulation of the PR-Set7 histone methyltransferase is required for normal cell cycle progression

2010 ◽  
Vol 24 (22) ◽  
pp. 2531-2542 ◽  
Author(s):  
S. Wu ◽  
W. Wang ◽  
X. Kong ◽  
L. M. Congdon ◽  
K. Yokomori ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Normal Cell ◽  
Cell Cycle Progression ◽  
Histone Methyltransferase ◽  
Cycle Progression ◽  
Dynamic Regulation ◽  
Normal Cell Cycle

scholarly journals Involvement of DNA-dependent Protein Kinase in Normal Cell Cycle Progression through Mitosis

2011 ◽  
Vol 286 (14) ◽  
pp. 12796-12802 ◽  
Author(s):  
Kyung-Jong Lee ◽  
Yu-Fen Lin ◽  
Han-Yi Chou ◽  
Hirohiko Yajima ◽  
Kazi R. Fattah ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Protein Kinase ◽  
Normal Cell ◽  
Cell Cycle Progression ◽  
Dependent Protein Kinase ◽  
Cycle Progression ◽  
Dependent Protein ◽  
Normal Cell Cycle

scholarly journals The highly conserved N-terminal domains of histones H3 and H4 are required for normal cell cycle progression

1991 ◽  
Vol 11 (8) ◽  
pp. 4111-4120
Author(s):  
B A Morgan ◽  
B A Mittman ◽  
M M Smith
Keyword(s):  
Cell Cycle ◽  
Normal Cell ◽  
Cell Cycle Progression ◽  
Histone H3 ◽  
Temperature Sensitive ◽  
Histone H4 ◽  
Cycle Progression ◽  
Terminal Domain ◽  
Normal Cell Cycle ◽  
Terminal Domains

The N-terminal domains of the histones H3 and H4 are highly conserved throughout evolution. Mutant alleles deleted for these N-terminal domains were constructed in vitro and examined for function in vivo in Saccharomyces cerevisiae. Cells containing a single deletion allele of either histone H3 or histone H4 were viable. Deletion of the N-terminal domain of histone H4 caused cells to become sterile and temperature sensitive for growth. The normal cell cycle progression of these cells was also altered, as revealed by a major delay in progression through the G2 + M periods. Deletion of the N-terminal domain of histone H3 had only minor effects on mating and the temperature-sensitive growth of mutant cells. However, like the H4 mutant, the H3 mutants had a significant delay in completing the G2 + M periods of the division cycle. Double mutants containing N-terminal domain deletions of both histone H3 and histone H4 were inviable. The phenotypes of cells subject to this synthetic lethality suggest that the N-terminal domains are required for functions essential throughout the cell division cycle and provide genetic evidence that histones are randomly distributed during chromosome replication.

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