A transcription co-factor integrates cell adhesion and motility with the p53 response

Coutts, Amanda S.; Weston, Louise; Thangué, Nicholas B. La

doi:10.1073/pnas.0906785106

Cited by 85 publications

(173 citation statements)

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“…One interesting example is JMY (junction-mediating and regulatory protein), a cytoplasmic actin-binding protein that can promote microfilament polymerization and directly interacts with p53 and p300/CBP. [84][85][86][87] After DNA damage, JMY accumulates in the nucleus, in which it associates with p53 and the tetratricopeptide repeat-containing protein STRAP to form a complex that includes p300/CBP, and promotes p53-dependent transcription and apoptosis. 84,87 Interestingly, STRAP can also recruit within this complex the arginine methylase PRMT5 that modifies three residues in the C-terminal region of p53.…”

Section: And References Therein)mentioning

confidence: 99%

p53-family proteins and their regulators: hubs and spokes in tumor suppression

2010

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The tumor suppressor p53 is a central hub in a molecular network controlling cell proliferation and death in response to potentially oncogenic conditions, and a wide array of covalent modifications and protein interactions modulate the nuclear and cytoplasmic activities of p53. The p53 relatives, p73 and p63, are entangled in the same regulatory network, being subject at least in part to the same modifications and interactions that convey signals on p53, and actively contributing to the resulting cellular output. The emerging picture is that of an interconnected pathway, in which all p53-family proteins are involved in the response to oncogenic stress and physiological inputs. Therefore, common and specific interactors of p53-family proteins can have a wide effect on function and dysfunction of this pathway. Many years of research have uncovered an impressive number of p53-interacting proteins, but much less is known about protein interactions of p63 and p73. Yet, many interactors may be shared by multiple p53-family proteins, with similar or different effects. In this study we review shared interactors of p53-family proteins with the aim to encourage research into this field; this knowledge promises to unveil regulatory elements that could be targeted by a new generation of molecules, and allow more efficient use of currently available drugs for cancer treatment.

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Section: And References Therein)mentioning

confidence: 99%

p53-family proteins and their regulators: hubs and spokes in tumor suppression

2010

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“…Upon DNA damage, it was observed that JMY interacts with and forms a complex with p300 and Strap while recruiting PRMT5 into a co-activator complex that triggers p53 response [10]. According to Coutts et.al JMY's functional role in p53 response is evident in its associated increase with p53-dependent transcription induced apoptosis.…”

Section: Introductionmentioning

confidence: 99%

“…JMY localizes both in nucleus and cytoplasm [11], but following stress or DNA damage JMY starts to migrate from the cytoplasm to accumulate in the nucleus [10]. Metastasis is facilitated by increased cell motility, allowing tumour cells to invade and colonize surrounding as well as distant tissues.…”

Section: Introductionmentioning

confidence: 99%

“…Metastasis is facilitated by increased cell motility, allowing tumour cells to invade and colonize surrounding as well as distant tissues. In addition to its role in p53 induced apoptosis, JMY also participates in the enhancement of cell motility [10]. JMY contains a series of WH2 domains that promote actin nucleation or elongation enabling it to promote cell motility [10].…”

Section: Introductionmentioning

confidence: 99%

“…In addition to its role in p53 induced apoptosis, JMY also participates in the enhancement of cell motility [10]. JMY contains a series of WH2 domains that promote actin nucleation or elongation enabling it to promote cell motility [10]. Studies have shown that JMY also nucleates actin in vitro and induces actin filament formation in vivo due its inherent WH2 domain series [10,12].…”

Section: Introductionmentioning

confidence: 99%

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The Role of JMY in p53 Regulation.

Adighibe¹

2018

Preprint

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Abstract:Following the event of DNA damage the levels of tumour suppressor protein p53 increases inducing either cell cycle arrest or apoptosis. Junctional Mediating and Regulating Y protein (JMY) is a transcription co-factor involved in p53 regulation. Hence in the event of DNA damage, JMY levels are also upregulated in the nucleus where JMY forms a complex with p300/CREB-binding protein (p300/CBP), Apoptosis-stimulating protein of p53 (ASPP) and Stress responsive activator of p53 (Strap). This co-activator complex then binds to and increases the ability of p53 to induce transcription of proteins triggering apoptosis but not cell cycle arrest. This then suggests that the increase of JMY levels due to DNA damage putatively "direct" p53 activity toward triggering apoptosis. JMY expression is also linked to increased cell motility as it: downregulates the expression of adhesion molecules of the Cadherin family and induces actin nucleation; making cells less adhesive and more mobile, favouring metastasis.All these characteristics taken together imply that JMY therefore possesses both tumour suppressive and tumour promoting capabilities.

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Actin on DNA—An ancient and dynamic relationship

Skarp

Vartiainen

2010

Cytoskeleton

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In the cytoplasm of eukaryotic cells the coordinated assembly of actin filaments drives essential cell biological processes, such as cell migration. The discovery of prokaryotic actin homologues, as well as the appreciation of the existence of nuclear actin, have expanded the scope by which the actin family is utilized in different cell types. In bacteria, actin has been implicated in DNA movement tasks, while the connection with the RNA polymerase machinery appears to exist in both prokaryotes and eukaryotes. Within the nucleus, actin has further been shown to play a role in chromatin remodeling and RNA processing, possibly acting to link these to transcription, thereby facilitating the gene expression process. The molecular mechanism by which actin exerts these newly discovered functions is still unclear, because while polymer formation seems to be required in bacteria, these species lack conventional actin-binding proteins to regulate the process. Furthermore, although the nucleus contains a plethora of actin-regulating factors, the polymerization status of actin within this compartment still remains unclear. General theme, however, seems to be actin's ability to interact with numerous binding partners. A common feature to the novel modes of actin utilization is the connection between actin and DNA, and here we aim to review the recent literature to explore how this connection is exploited in different contexts. V C 2010 Wiley-Liss, Inc.Key Words: actin, myosin, DNA, nucleus, transcription Introduction S ince the discovery of actin, a great number of actin-binding proteins (ABPs) have been found and implicated in various cellular processes. Traditionally, the reign of actin and ABPs has been limited to the cytoplasm, where they cooperate to form helical actin filaments, which can be bundled and cross-linked to different structural ends. The coordinated assembly of these filaments then drives for example cell migration, cytokinesis and membrane dynamics [reviewed in Pollard and Borisy, 2003]. However, during the past decade, actin has been transformed from an exclusively cytoskeletal component in eukaryotic cells to a multipurpose tool that most cells use in a number of processes. Especially the discovery of a function for actin in the nucleus [reviewed in Vartiainen, 2008] and identification of prokaryotic actin homologues [van den Ent et al., 2001] has yielded surprising data, which has considerably expanded the modes by which the actin family is utilized in different functional contexts. In the nucleus, actin has been shown to be involved all the way in the gene expression process from chromatin remodeling complexes through transcription to spliceosome function and mRNA export [reviewed in Percipalle, 2009]. In addition, nuclear actin also seems to affect the expression of subsets of genes by regulating the activity of specific transcription factors [Vartiainen et al., 2007]. However, the biochemical details of most of these actin-involving processes are lacking, and the nature and mechanics of the interact...

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A transcription co-factor integrates cell adhesion and motility with the p53 response

Cited by 85 publications

References 49 publications

p53-family proteins and their regulators: hubs and spokes in tumor suppression

p53-family proteins and their regulators: hubs and spokes in tumor suppression

The Role of JMY in p53 Regulation.

Actin on DNA—An ancient and dynamic relationship

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