scholarly journals Beyond HAT Adaptor: TRRAP Liaisons with Sp1-Mediated Transcription

2021 ◽  
Vol 22 (22) ◽  
pp. 12445
Author(s):  
Bo-Kun Yin ◽  
Zhao-Qi Wang
Keyword(s):  
Transcription Factors ◽  
Cell Cycle Progression ◽  
Histone Acetyltransferase ◽  
Adaptor Protein ◽  
Biological Processes ◽  
Phosphatidylinositol 3 Kinase ◽  
Cellular Functions ◽  
Cycle Progression ◽  
Action Mode ◽  
Damage Response

The members of the phosphatidylinositol 3-kinase-related kinase (PIKK) family play vital roles in multiple biological processes, including DNA damage response, metabolism, cell growth, mRNA decay, and transcription. TRRAP, as the only member lacking the enzymatic activity in this family, is an adaptor protein for several histone acetyltransferase (HAT) complexes and a scaffold protein for multiple transcription factors. TRRAP has been demonstrated to regulate various cellular functions in cell cycle progression, cell stemness maintenance and differentiation, as well as neural homeostasis. TRRAP is known to be an important orchestrator of many molecular machineries in gene transcription by modulating the activity of some key transcription factors, including E2F1, c-Myc, p53, and recently, Sp1. This review summarizes the biological and biochemical studies on the action mode of TRRAP together with the transcription factors, focusing on how TRRAP-HAT mediates the transactivation of Sp1-governing biological processes, including neurodegeneration.

scholarly journals Targeting Protein-Protein Interactions in the DNA Damage Response Pathways for Cancer Chemotherapy

2021 ◽  
Author(s):  
Kerry Silva McPherson ◽  
Dmitry Korzhnev
Keyword(s):  
Dna Damage ◽  
Dna Damage Response ◽  
Protein Interactions ◽  
Cell Cycle Progression ◽  
Protein Protein Interactions ◽  
Cycle Progression ◽  
Damage Recognition ◽  
Damage Response ◽  
Cellular Dna ◽  
Dna Damage Recognition

Cellular DNA damage response (DDR) is an extensive signaling network that orchestrates DNA damage recognition, repair and avoidance, cell cycle progression and cell death. DDR alternation is a hallmark of...

scholarly journals Overall Cdk activity modulates the DNA damage response in mammalian cells

2009 ◽  
Vol 187 (6) ◽  
pp. 773-780 ◽  
Author(s):  
Antonio Cerqueira ◽  
David Santamaría ◽  
Bárbara Martínez-Pastor ◽  
Miriam Cuadrado ◽  
Oscar Fernández-Capetillo ◽  
...  
Keyword(s):  
Dna Damage ◽  
Dna Damage Response ◽  
Mammalian Cells ◽  
Cell Cycle Progression ◽  
Cyclin Dependent Kinase ◽  
Genome Maintenance ◽  
Cycle Progression ◽  
Damage Response ◽  
Dna Break ◽  
Specific Contribution

In response to DNA damage, cells activate a phosphorylation-based signaling cascade known as the DNA damage response (DDR). One of the main outcomes of DDR activation is inhibition of cyclin-dependent kinase (Cdk) activity to restrain cell cycle progression until lesions are healed. Recent studies have revealed a reverse connection by which Cdk activity modulates processing of DNA break ends and DDR activation. However, the specific contribution of individual Cdks to this process remains poorly understood. To address this issue, we have examined the DDR in murine cells carrying a defined set of Cdks. Our results reveal that genome maintenance programs of postreplicative cells, including DDR, are regulated by the overall level of Cdk activity and not by specific Cdks.

scholarly journals Ras controls growth, survival and differentiation in the Drosophila eye by different thresholds of MAP kinase activity

Development ◽  
2001 ◽  
Vol 128 (9) ◽  
pp. 1687-1696 ◽  
Author(s):  
K. Halfar ◽  
C. Rommel ◽  
H. Stocker ◽  
E. Hafen
Keyword(s):  
Cell Cycle ◽  
Cell Cycle Progression ◽  
Kinase Activity ◽  
Photoreceptor Cells ◽  
Loss Of Function ◽  
Cellular Functions ◽  
Partial Loss ◽  
Cycle Progression ◽  
Mapk Activity ◽  
Dividing Cells

Ras mediates a plethora of cellular functions during development. In the developing eye of Drosophila, Ras performs three temporally separate functions. In dividing cells, it is required for growth but is not essential for cell cycle progression. In postmitotic cells, it promotes survival and subsequent differentiation of ommatidial cells. In the present paper, we have analyzed the different roles of Ras during eye development by using molecularly defined complete and partial loss-of-function mutations of Ras. We show that the three different functions of Ras are mediated by distinct thresholds of MAPK activity. Low MAPK activity prolongs cell survival and permits differentiation of R8 photoreceptor cells while high or persistent MAPK activity is sufficient to precociously induce R1-R7 photoreceptor differentiation in dividing cells.

scholarly journals Regulation of KAT6 Acetyltransferases and Their Roles in Cell Cycle Progression, Stem Cell Maintenance, and Human Disease

2016 ◽  
Vol 36 (14) ◽  
pp. 1900-1907 ◽  
Author(s):  
Fu Huang ◽  
Susan M. Abmayr ◽  
Jerry L. Workman
Keyword(s):  
Cell Cycle ◽  
Stem Cell ◽  
Cell Cycle Progression ◽  
Histone Acetyltransferase ◽  
Regulatory Mechanisms ◽  
Cycle Progression ◽  
Stem Cell Maintenance ◽  
Lysine Acetyltransferase ◽  
Cycle Regulation ◽  
Cell Maintenance

The lysine acetyltransferase 6 (KAT6) histone acetyltransferase (HAT) complexes are highly conserved from yeast to higher organisms. They acetylate histone H3 and other nonhistone substrates and are involved in cell cycle regulation and stem cell maintenance. In addition, the human KAT6 HATs are recurrently mutated in leukemia and solid tumors. Therefore, it is important to understand the mechanisms underlying the regulation of KAT6 HATs and their roles in cell cycle progression. In this minireview, we summarize the identification and analysis of the KAT6 complexes and discuss the regulatory mechanisms governing their enzymatic activities and substrate specificities. We further focus on the roles of KAT6 HATs in regulating cell proliferation and stem cell maintenance and review recent insights that aid in understanding their involvement in human diseases.

scholarly journals Regulation of Focal Adhesion Kinase by a Novel Protein Inhibitor FIP200

2002 ◽  
Vol 13 (9) ◽  
pp. 3178-3191 ◽  
Author(s):  
Smita Abbi ◽  
Hiroki Ueda ◽  
Chuanhai Zheng ◽  
Lee Ann Cooper ◽  
Jihe Zhao ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Focal Adhesion Kinase ◽  
Focal Adhesion ◽  
Cell Cycle Progression ◽  
Protein Inhibitor ◽  
Cellular Functions ◽  
Cycle Progression ◽  
Novel Protein

Focal adhesion kinase (FAK) is a major mediator of integrin signaling pathways. The mechanisms of regulation of FAK activity and its associated cellular functions are not very well understood. Here, we present data suggesting that a novel protein FIP200 functions as an inhibitor for FAK. We show the association of endogenous FIP200 with FAK, which is decreased upon integrin-mediated cell adhesion concomitant with FAK activation. In vitro- and in vivo-binding studies indicate that FIP200 interacts with FAK through multiple domains directly. FIP200 bound to the kinase domain of FAK inhibited its kinase activity in vitro and its autophosphorylation in vivo. Overexpression of FIP200 or its segments inhibited cell spreading, cell migration, and cell cycle progression, which correlated with their inhibition of FAK activity in vivo. The inhibition of these cellular functions by FIP200 could be rescued by coexpression of FAK. Last, we show that disruption of the functional interaction between endogenous FIP200 with FAK leads to increased FAK phosphorylation and partial restoration of cell cycle progression in cells plated on poly-l-lysine, providing further support for FIP200 as a negative regulator of FAK. Together, these results identify FIP200 as a novel protein inhibitor for FAK.

scholarly journals Structural mechanism of Myb–MuvB assembly

2018 ◽  
Vol 115 (40) ◽  
pp. 10016-10021 ◽  
Author(s):  
Keelan Z. Guiley ◽  
Audra N. Iness ◽  
Siddharth Saini ◽  
Sarvind Tripathi ◽  
Joseph S. Lipsick ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Cell Cycle Progression ◽  
Biochemical Analysis ◽  
Adaptor Protein ◽  
Cancer Cell Proliferation ◽  
Cycle Progression ◽  
Structural Mechanism ◽  
Transcriptional Regulatory ◽  
Regulatory Complex ◽  
Cycle Dependent

The MuvB transcriptional regulatory complex, which controls cell-cycle-dependent gene expression, cooperates with B-Myb to activate genes required for the G2 and M phases of the cell cycle. We have identified the domain in B-Myb that is essential for the assembly of the Myb–MuvB (MMB) complex. We determined a crystal structure that reveals how this B-Myb domain binds MuvB through the adaptor protein LIN52 and the scaffold protein LIN9. The structure and biochemical analysis provide an understanding of how oncogenic B-Myb is recruited to regulate genes required for cell-cycle progression, and the MMB interface presents a potential therapeutic target to inhibit cancer cell proliferation.

scholarly journals The Licensing Factor Cdt1 Links Cell Cycle Progression to the DNA Damage Response

2020 ◽  
Vol 40 (5) ◽  
pp. 2449-2456
Author(s):  
ALEXANDRA KANELLOU ◽  
NICKOLAOS NIKIFOROS GIAKOUMAKIS ◽  
ANDREAS PANAGOPOULOS ◽  
SPYRIDON CHAMPERIS TSANIRAS ◽  
ZOI LYGEROU
Keyword(s):  
Cell Cycle ◽  
Dna Damage ◽  
Dna Damage Response ◽  
Cell Cycle Progression ◽  
Cycle Progression ◽  
Damage Response ◽  
Licensing Factor
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