Systematic Identification of Molecular Links between Core and Candidate Genes in Breast Cancer

Arroyo, Rodrigo; Suñé, Guillermo; Zanzoni, Andreas; Duran‐Frigola, Miquel; Alcalde, Víctor; Stracker, Travis H.; Soler-López, Montserrat; Aloy, Patrick

doi:10.1016/j.jmb.2015.01.014

Cited by 17 publications

(15 citation statements)

References 71 publications

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“…Since Bex1 has been shown to interact with many different proteins, several potential mechanisms, independent of p75 NTR signaling, are suggested by previous work. For example, BEX1 has been reported to bind Calmodulin (65), BAG4/SODD, and Caspase 8 (70), all of which have roles in death signaling through DISC (71)(72)(73). In contrast to our observations, Bex1 has been shown to have a pro-apoptotic role by binding to Bcl2 in cancer cells (74).…”

Section: Discussioncontrasting

confidence: 87%

“…However, it is unclear what role the cellular context plays in determining the downstream outcome of this interaction. Bex family proteins have also been shown (70,75) to interact with several common proteins -RAD51, ATM, AKT, AURKA, c-JUN, CHEK2 -as does BRCA1, which regulates DNA damage through the BASC complex (76), and is required for CCNE1 amplified tumors (77). Alternatively, Bex1 interactor Pax2 (70) has been shown to regulate retinoblastoma protein (78), a particularly interesting observation given the role of RB in controlling E2F2 activity.…”

Section: Discussionmentioning

confidence: 99%

“…Bex family proteins have also been shown (70,75) to interact with several common proteins -RAD51, ATM, AKT, AURKA, c-JUN, CHEK2 -as does BRCA1, which regulates DNA damage through the BASC complex (76), and is required for CCNE1 amplified tumors (77). Alternatively, Bex1 interactor Pax2 (70) has been shown to regulate retinoblastoma protein (78), a particularly interesting observation given the role of RB in controlling E2F2 activity. Moreover, BEX1 binds FBXW7 (70), an Fbox protein which promotes Cyclin E degradation through the SKP1-Cullin1-F-BOX (SCF) E3 ligase complex (79).…”

Section: Discussionmentioning

confidence: 99%

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Defined factors to reactivate cell cycle activity in adult mouse cardiomyocytes

Judd

Lovas

Huang

2019

Preprint

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Adult mammalian cardiomyocytes exit the cell cycle during the neonatal period, commensurate with the loss of regenerative capacity in adult mammalian hearts. We established conditions for long-term culture of adult mouse cardiomyocytes that are genetically labeled with fluorescence. This technique permits reliable analyses of proliferation of pre-existing cardiomyocytes without complications from cardiomyocyte marker expression loss due to dedifferentiation or significant contribution from cardiac progenitor cell expansion and differentiation in culture.Using this system, we took a candidate gene approach to screen for fetal-specific proliferative gene programs that can induce proliferation of adult mouse cardiomyocytes. Using pooled gene delivery and subtractive gene elimination, we identified a novel functional interaction between E2f Transcription Factor 2 (E2f2) and Brain Expressed X-Linked (Bex)/Transcription elongation factor A-like (Tceal) superfamily members Bex1 and Tceal8. Specifically, Bex1 and Tceal8 both preserved cell viability during E2f2-induced cell cycle re-entry. Although Tceal8 inhibited E2f2-induced S-phase re-entry, Bex1 facilitated DNA synthesis while inhibiting cell death. In sum, our study provides a valuable method for adult cardiomyocyte proliferation research and suggests that Bex family proteins may function in modulating cell proliferation and death decisions during cardiomyocyte development and maturation.Real-time PCR showed that expression of endogenous positive cell cycle regulators Cyclin A2 and Cyclin E were induced by ectopic E2f2 expression, in agreement with

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Section: Discussioncontrasting

confidence: 87%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

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Defined factors to reactivate cell cycle activity in adult mouse cardiomyocytes

Judd

Lovas

Huang

2019

Preprint

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“…We observed that phosphorylation by Akt, Id2 acts as an ERM binding protein, which bound F-actin and enriched the peripheral region of growth cone, while unphosphorylated Id2 predominantly localized in the central region of the growth cone where growing microtubule directed to actin network and, among Id family members (Id1-Id4), only Id2 possesses a SxIP motif-specific sequence to enable its interaction with end binding (EB) proteins and the most prominent microtubule (MT) plus end binding protein (+TIP), which promotes MT dynamicity and growth (Coles and Bradke, 2015); thus, it is possible to conjecture that Id2 may act as +TIP thereby capable to crosslink the two filaments, actin and microtubule, during axon growth. Two independent studies (Arroyo et al, 2015; Huttlin et al, 2015), have speculated that both Akt1 and Id2 are interacting partners of cytoplasmic linker associated protein 2 (CLASP2), which is known to act +TIP (Beffert et al, 2012). Moreover, in addition to radixin, Id2 also interacts with actin-associated enigma homolog (ENH) and is sequestered into the cytoplasm from nucleus during neural differentiation (Lasorella and Iavarone, 2006).…”

Section: Discussionmentioning

confidence: 99%

Akt1-Inhibitor of DNA binding2 is essential for growth cone formation and axon growth and promotes central nervous system axon regeneration

Kwon

Hwang

et al. 2016

eLife

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Mechanistic studies of axon growth during development are beneficial to the search for neuron-intrinsic regulators of axon regeneration. Here, we discovered that, in the developing neuron from rat, Akt signaling regulates axon growth and growth cone formation through phosphorylation of serine 14 (S14) on Inhibitor of DNA binding 2 (Id2). This enhances Id2 protein stability by means of escape from proteasomal degradation, and steers its localization to the growth cone, where Id2 interacts with radixin that is critical for growth cone formation. Knockdown of Id2, or abrogation of Id2 phosphorylation at S14, greatly impairs axon growth and the architecture of growth cone. Intriguingly, reinstatement of Akt/Id2 signaling after injury in mouse hippocampal slices redeemed growth promoting ability, leading to obvious axon regeneration. Our results suggest that Akt/Id2 signaling is a key module for growth cone formation and axon growth, and its augmentation plays a potential role in CNS axonal regeneration.DOI: http://dx.doi.org/10.7554/eLife.20799.001

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“…Clustering algorithms developed for community detection are frequently based on graph topological properties, such as density or modularity (for reviews, Wang et al, 2010;Pizzuti and Rombo, 2014). They have been thoroughly assessed on biological networks (Brohée and van Helden, 2006), and are widely used in biology (Arroyo et al, 2015;Wan et al, 2015;Huttlin et al, 2015;Chapple et al, 2015;Katsogiannou et al, 2014). However, they have been applied on single networks whereas recently multiplex (alt.…”

Section: Introductionmentioning

confidence: 99%

Peer Review #1 of "Identifying communities from multiplex biological networks (v0.1)"

2015

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Various biological networks can be constructed, each featuring gene/protein relationships of different meanings (e.g. protein interactions or gene co-expression). However, this diversity is classically not considered and the different interaction categories are usually aggregated in a single network. The multiplex framework, where biological relationships are represented by different network layers reflecting the various nature of interactions, is expected to retain more information. We assessed here aggregation, consensus and multiplex-modularity approaches to detect communities from multiple network sources. By simulating random networks, we demonstrated that the multiplex-modularity method outperforms the aggregation and consensus approaches when network layers are incomplete or heterogeneous in density. Application to a multiplex biological network containing 4 layers of physical or functional interactions allowed recovering communities more accurately annotated than their aggregated counterparts. Overall, taking into account the multiplexity of biological networks leads to better-defined functional modules.

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Systematic Identification of Molecular Links between Core and Candidate Genes in Breast Cancer

Cited by 17 publications

References 71 publications

Defined factors to reactivate cell cycle activity in adult mouse cardiomyocytes

Defined factors to reactivate cell cycle activity in adult mouse cardiomyocytes

Akt1-Inhibitor of DNA binding2 is essential for growth cone formation and axon growth and promotes central nervous system axon regeneration

Peer Review #1 of "Identifying communities from multiplex biological networks (v0.1)"

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