Evidence for a Structural Relationship between BRCT Domains and the Helicase Domains of the Replication Initiators Encoded by the Polyomaviridae and Papillomaviridae Families of DNA Tumor Viruses

ABSTRACT Studies of DNA tumor viruses have provided important insights into fundamental cellular processes and oncogenic transformation. They have revealed, for example, that upon expression of virally encoded proteins, cellular pathways involved in DNA repair and cell cycle control are disrupted. Herein, evidence is presented that BRCT-related regions are present in the helicase domains of the viral initiators encoded by the Polyomaviridae and Papillomaviridae viral families. Of interest, BRCT domains in cellular proteins recruit factors involved in diverse pathways, including DNA repair and the regulation of cell cycle progression. Therefore, the viral BRCT-related regions may compete with host BRCT domains for particular cellular ligands, a process that would help to explain the pleiotropic effects associated with infections with many DNA tumor viruses.

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Regulation of cell cycle drivers by Cullin-RING ubiquitin ligases

Experimental & Molecular Medicine ◽

10.1038/s12276-020-00508-4 ◽

2020 ◽

Vol 52 (10) ◽

pp. 1637-1651 ◽

Cited By ~ 1

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.

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Cdk1-Dependent Phosphorylation ofNPM Overrides G2/M Checkpoint and Increases Leukemic Blasts in Mice

Blood ◽

10.1182/blood.v112.11.1322.1322 ◽

2008 ◽

Vol 112 (11) ◽

pp. 1322-1322

Author(s):

Wei Du ◽

Yun Zhou ◽

Suzette Pike ◽

Qishen Pang

Keyword(s):

Cell Cycle ◽

Cell Cycle Progression ◽

Cell Cycle Control ◽

Xenograft Model ◽

Phosphorylation Sites ◽

M Cell ◽

Cycle Progression ◽

Hematopoietic Stem ◽

Cycle Arrest ◽

Regulation Of Cell Cycle

Abstract An elevated level of nucleophosmin (NPM) is often found in actively proliferative cells including human tumors. To identify the regulatory role for NPM phosphorylation in proliferation and cell cycle control, a series of mutants targeting the consensus cyclin-dependent kinase (CKD) phosphorylation sites was created to mimic or abrogate either single-site or multi-site phosphorylation. Cells expressing the phosphomimetic NPM mutants showed enhanced proliferation and G2/M cell-cycle transition; whereas nonphosphorylatable mutants induced G2/M cell-cycle arrest. Simultaneous inactivation of two CKD phosphorylation sites at Ser10 and Ser70 (S10A/S70A, NPM-AA) induced phosphorylation of Cdk1 at Tyr15 (Cdc2Tyr15) and increased cytoplasmic accumulation of Cdc25C. Strikingly, stress-induced Cdk1Tyr15 and Cdc25C sequestration were completely suppressed by expression of a double phosphomimetic NPM mutant (S10E/S70E, NPM-EE). Further analysis revealed that phosphorylation of NPM at both Ser10 and Ser70 sites were required for proper interaction between Cdk1 and Cdc25C in mitotic cells. Moreover, the NPM-EE mutant directly bound to Cdc25C and prevented phosphorylation of Cdc25C at Ser216 during mitosis. Finally, NPM-EE overrided stress-induced G2/M arrest, increased peripheral-blood blasts and splenomegaly in a NOD/SCID xenograft model, and promoted leukemia development in Fanconi mouse hematopoietic stem/progenitor cells. Thus, these findings reveal a novel function of NPM on regulation of cell-cycle progression, in which Cdk1-dependent phosphorylation of NPM controls cell-cycle progression at G2/M transition through modulation of Cdc25C activity.

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E2f4 regulates fetal erythropoiesis through the promotion of cellular proliferation

Blood ◽

10.1182/blood-2005-09-008656 ◽

2006 ◽

Vol 108 (3) ◽

pp. 886-895 ◽

Cited By ~ 50

Author(s):

Kathryn M. Kinross ◽

Allison J. Clark ◽

Rosa M. Iazzolino ◽

Patrick Orson Humbert

Keyword(s):

Cell Cycle ◽

Cell Cycle Progression ◽

Cellular Proliferation ◽

Cell Cycle Control ◽

Macrocytic Anemia ◽

Cycle Progression ◽

Promote Cell Cycle Progression ◽

Regulation Of Cell Cycle ◽

Fetal Erythropoiesis

Abstract The E2F proteins are major regulators of the transcriptional program required to coordinate cell cycle progression and exit. In particular, E2f4 has been proposed to be the principal family member responsible for the regulation of cell cycle exit chiefly through its transcriptional repressive properties. We have previously shown that E2f4–/– mice display a marked macrocytic anemia implicating E2f4 in the regulation of erythropoiesis. However, these studies could not distinguish whether E2f4 was required for differentiation, survival, or proliferation control. Here, we describe a novel function for E2f4 in the promotion of erythroid proliferation. We show that loss of E2f4 results in an impaired expansion of the fetal erythroid compartment in vivo that is associated with impaired cell cycle progression and decreased erythroid proliferation. Consistent with these observations, cDNA microarray analysis reveals cell cycle control genes as one of the major class of genes down-regulated in E2f4–/– FLs, and we provide evidence that E2f4 may directly regulate the transcriptional expression of a number of these genes. We conclude that the macrocytic anemia of E2f4–/– mice results primarily from impaired cellular proliferation and that the major role of E2f4 in fetal erythropoiesis is to promote cell cycle progression and cellular proliferation.

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Emerging concepts of nucleolar assembly

Journal of Cell Science ◽

10.1242/jcs.115.11.2265 ◽

2002 ◽

Vol 115 (11) ◽

pp. 2265-2270 ◽

Cited By ~ 4

Author(s):

Danièle Hernandez-Verdun ◽

Pascal Roussel ◽

Jeannine Gébrane-Younès

Keyword(s):

Cell Cycle ◽

Ribosome Biogenesis ◽

Cell Cycle Progression ◽

Cell Cycle Control ◽

Cycle Progression ◽

Cooperative Interactions ◽

Cellular Processes ◽

Nuclear Domain ◽

New Ideas

The nucleolus is a large nuclear domain and the site of ribosome biogenesis. It is also at the parting of the ways of several cellular processes, including cell cycle progression, gene silencing, and ribonucleoprotein complex formation. Consequently, a functional nucleolus is crucial for cell survival. Recent investigations of nucleolar assembly during the cell cycle and during embryogenesis have provided an integrated view of the dynamics of this process. Moreover, they have generated new ideas about cell cycle control of nucleolar assembly, the dynamics of the delivery of the RNA processing machinery, the formation of prenucleolar bodies, the role of precursor ribosomal RNAs in stabilizing the nucleolar machinery and the fact that nucleolar assembly is completed by cooperative interactions between chromosome territories. This has opened a new area of research into the dynamics of nuclear organization and the integration of nuclear functions.

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Faculty Opinions recommendation of E2F integrates cell cycle progression with DNA repair, replication, and G(2)/M checkpoints.

Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature ◽

10.3410/f.1005538.71460 ◽

2002 ◽

Author(s):

Michael Meisterernst

Keyword(s):

Cell Cycle ◽

Dna Repair ◽

Cell Cycle Progression ◽

Cycle Progression

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Differential Regulation of Cell Cycle Progression in Human Breast Cancer Cell Lines by the Estrogen Receptor

10.21236/ada394036 ◽

2000 ◽

Author(s):

James Direnzo ◽

Myles Brown

Keyword(s):

Breast Cancer ◽

Cell Cycle ◽

Human Breast Cancer ◽

Cell Cycle Progression ◽

Differential Regulation ◽

Human Breast Cancer Cell ◽

Breast Cancer Cell Lines ◽

Human Breast ◽

Cycle Progression ◽

Regulation Of Cell Cycle

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PTTG has a Dual Role of Promotion-Inhibition in the Development of Pituitary Adenomas

Protein and Peptide Letters ◽

10.2174/0929866526666190722145449 ◽

2019 ◽

Vol 26 (11) ◽

pp. 800-818

Author(s):

Zujian Xiong ◽

Xuejun Li ◽

Qi Yang

Keyword(s):

Cell Cycle ◽

Pituitary Adenoma ◽

Pituitary Adenomas ◽

Cell Cycle Progression ◽

Key Factors ◽

Cycle Progression ◽

Sister Chromatids ◽

Regulation Of Cell Cycle ◽

Late Stages

Pituitary Tumor Transforming Gene (PTTG) of human is known as a checkpoint gene in the middle and late stages of mitosis, and is also a proto-oncogene that promotes cell cycle progression. In the nucleus, PTTG works as securin in controlling the mid-term segregation of sister chromatids. Overexpression of PTTG, entering the nucleus with the help of PBF in pituitary adenomas, participates in the regulation of cell cycle, interferes with DNA repair, induces genetic instability, transactivates FGF-2 and VEGF and promotes angiogenesis and tumor invasion. Simultaneously, overexpression of PTTG induces tumor cell senescence through the DNA damage pathway, making pituitary adenoma possessing the potential self-limiting ability. To elucidate the mechanism of PTTG in the regulation of pituitary adenomas, we focus on both the positive and negative function of PTTG and find out key factors interacted with PTTG in pituitary adenomas. Furthermore, we discuss other possible mechanisms correlate with PTTG in pituitary adenoma initiation and development and the potential value of PTTG in clinical treatment.

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