Modeling oscillatory control in NF-κB, p53 and Wnt signaling

Mengel, Benedicte; Hunziker, Alexander; Pedersen, Lykke; Trusina, Ala; Jensen, Mogens H.; Krishna, Sandeep

doi:10.1016/j.gde.2010.08.008

Cited by 67 publications

(53 citation statements)

References 70 publications

(45 reference statements)

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“…NF-κB induces the expression of genes that are known to confer resistance to apoptosis and is indirectly regulated by calcium homeostasis (51). The oscillation of calcium is known to play a key role in the oscillatory regulations of NF-κB, p53, and Wnt signaling (52). A tissue-type transglutaminase (TG2), the most diverse and ubiquitous member of the calciumdependent transglutaminase family of enzymes, which can activate NF-κB, is also aberrantly overexpressed in many human cancer types, blocks apoptosis, and promotes drug resistance and metastatic phenotypes (53).…”

Section: +mentioning

confidence: 99%

TRPV6 calcium channel translocates to the plasma membrane via Orai1-mediated mechanism and controls cancer cell survival

Raphaël

Lehen’kyi

Vandenberghe

et al. 2014

Proc. Natl. Acad. Sci. U.S.A.

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Transient receptor potential vanilloid subfamily member 6 (TRPV6) is a highly selective calcium channel that has been considered as a part of store-operated calcium entry (SOCE). Despite its first discovery in the early 2000s, the role of this channel in prostate cancer (PCa) remained, until now, obscure. Here we show that TRPV6 mediates calcium entry, which is highly increased in PCa due to the remodeling mechanism involving the translocation of the TRPV6 channel to the plasma membrane via the Orai1/TRPC1-mediated Ca 2+

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Section: +mentioning

confidence: 99%

TRPV6 calcium channel translocates to the plasma membrane via Orai1-mediated mechanism and controls cancer cell survival

Raphaël

Lehen’kyi

Vandenberghe

et al. 2014

Proc. Natl. Acad. Sci. U.S.A.

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“…In all these cases, the very physical reason for time oscillations was found to be a delay in some elements of the control network of these proteins [10][11][12] (for a review, see refs. [13,14]). …”

Section: Introductionmentioning

confidence: 99%

The dynamics of genetic control in the cell: the good and bad of being late

Tiana

Jensen

2013

Phil. Trans. R. Soc. A.

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One contribution of 15 to a Theme Issue 'Dynamics, control and information in delay-coupled systems' . The expression of genes in the cell is controlled by a complex interaction network involving proteins, RNA and DNA. The molecular events associated with the nodes of such a network take place on a variety of time scales, and thus cannot be regarded as instantaneous. In many cases, the cell is robust with respect to the delay in gene expression control, behaving as if it were instantaneous. However, there are specific cases in which delay gives rise to temporal oscillations. This is the case, for example, of the expression of tumoursuppressor protein p53, of protein Hes1, involved in the differentiation of stem cells, of NFkB and Wnt, in which case delay arises implicitly from the structure of the associated network. By means of delay rate equations, we study the kinetics of small regulatory networks, emphasizing the role of delay in an evolutionary context. These models suggest that oscillations are a typical outcome of the dynamics of regulatory networks, and evolution has to work to avoid them when not required (and not vice versa).

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“…Thus, many studies have aimed to uncover the dynamical design principles of such modules, viewed as building blocks for larger systems or as devices for synthetic biology. For example, the appearance of oscillations has been linked to negative feedback and time delays [2], and the importance of mechanisms such as complexation [4] or saturated degradation [5][6][7] for oscillations has been highlighted.…”

mentioning

confidence: 99%

“…Recent studies (see [8] for a review) revealed that also signaling proteins, which detect and deliver cellular signals, can display oscillating dynamics. In some systems, oscillations appear as discrete pulses separated by constant time intervals [9], while in others the intensity of upstream signals determines the time interval between pulses [10,11], which may thus be used to encode information [7]. A natural question is then whether we can identify simple model systems that display similar behavior.…”

mentioning

confidence: 99%

“…A striking feature of the HAL is that the duration of the the A-pulses is robust against variation of the rate constants, whereas the duration of the B-pulses is tunable. It has been suggested that biological signals may be encoded in time interval between pulses [7][8][9][10][11]. Since the HAL is a robust and flexible pulse generator, it would perfectly fit into this design.…”

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confidence: 99%

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Heterodimer Autorepression Loop: A Robust and Flexible Pulse-Generating Genetic Module

2016

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We investigate the dynamics of the heterodimer autorepression loop (HAL), a small genetic module in which a protein A acts as an auto-repressor and binds to a second protein B to form a AB dimer. For suitable values of the rate constants the HAL produces pulses of A alternating with pulses of B. By means of analytical and numerical calculations, we show that the duration of A-pulses is extremely robust against variation of the rate constants while the duration of the B-pulses can be flexibly adjusted. The HAL is thus a minimal genetic module generating robust pulses with tunable duration an interesting property for cellular signalling.

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Modeling oscillatory control in NF-κB, p53 and Wnt signaling

Cited by 67 publications

References 70 publications

TRPV6 calcium channel translocates to the plasma membrane via Orai1-mediated mechanism and controls cancer cell survival

TRPV6 calcium channel translocates to the plasma membrane via Orai1-mediated mechanism and controls cancer cell survival

The dynamics of genetic control in the cell: the good and bad of being late

Heterodimer Autorepression Loop: A Robust and Flexible Pulse-Generating Genetic Module

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