RASSF3 and NORE1: identification and cloning of two human homologues of the putative tumor suppressor gene RASSF1

Tommasi, Stefania; Dammann, Reinhard; Jin, Seung-Gi; Zhang, Xianfeng; Avruch, Joseph; Pfeifer, Gerd P.

doi:10.1038/sj.onc.1205365

Cited by 102 publications

(108 citation statements)

References 36 publications

(38 reference statements)

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“…Consistent with earlier reports [20,28], we find Nore1B to be the dominant isoform expressed in T cells (Fig. 1D); in as much as Carma1 is critical for TCR-induced NF-κB activation [29], we next investigated the involvement of Nore1B in NF-κB activation in Jurkat cells.…”

Section: Nore1a and 1b Bind To Carma1supporting

confidence: 70%

Nore1B regulates TCR signaling via Ras and Carma1

Ishiguro

Avruch

Landry

et al. 2006

Cellular Signalling

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Nore1A was originally identified as a potential Ras effector, and Nore1B is an alternatively spliced isoform. Both share a Ras/Rap association domain (RA domain) but only Nore1A contains sequence motifs that predict SH3 domain binding and diacylglycerol/phorbol ester binding in the amino-terminal region. Here we report that Carma1 binds to Nore1A and Nore1B through the RA domain and that Carma1 interacts with active Ras in the presence of Nore1B. RNA interference against Nore1B attenuates NF-κB activation induced by T cell receptor (TCR) ligation, but not NF-κB activation induced by TNFα or lipoteichoic acid. In addition, Nore1B is also required for KiRas GV12-mediated ERK1 activation and Elk1 reporter activity in T cells. We also provide evidence that knockdown of Nore1B also impairs polarized redistribution of Ras at the B cell-T cell immune interface. Together, these findings suggest that endogenous Nore1B recruits active Ras to the APC-T cell interface and mediates the interaction between Ras and Carma1.

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Section: Nore1a and 1b Bind To Carma1supporting

confidence: 70%

Nore1B regulates TCR signaling via Ras and Carma1

Ishiguro

Avruch

Landry

et al. 2006

Cellular Signalling

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“…CNK1-(1-282) and CNK1-(199 -713) were PCR-amplified using CNK1 as a template and similarly cloned into the pEAK8-Myc vector. RASSF1A, RASSF1C, MST1 (and fragments), and MST2 were cloned in pCMV-FLAG as described earlier (10,15).…”

Section: Methodsmentioning

confidence: 99%

“…A fraction of this kinase is found in complexes with the proteins NORE1 and RASSF1. The latter are noncatalytic polypeptides, each expressed as several isoforms that contain variable amino termini but a homologous carboxyl-terminal segment encompassing a Ras association (RA) 1 domain followed by a conserved carboxyl terminus (7)(8)(9)(10), recently designated as a SARAH domain (11); the NORE RA domain 1 The abbreviations used are: RA, Ras association; CMV, cytomegalovirus; PBS, phosphate-buffered saline; RIPA, radioimmune precipitation assay buffer; GFP, green fluorescent protein; X-Gal, 5-bromo-4-chloro-3-indolyl-␤-D-galactoside; CNK, connector enhancer of KSR; MST, mammalian sterile 20 kinases.…”

mentioning

confidence: 99%

The Scaffold Protein CNK1 Interacts with the Tumor Suppressor RASSF1A and Augments RASSF1A-induced Cell Death

Rabizadeh

Xavier

Ishiguro

et al. 2004

Journal of Biological Chemistry

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The connector enhancer of KSR (CNK) is a multidomain scaffold protein discovered in Drosophila, where it is necessary for Ras activation of the Raf kinase. Recent studies have shown that CNK1 also interacts with RalA and Rho and participates in some aspects of signaling by these GTPases. Herein we demonstrate a novel aspect of CNK1 function, i.e. reexpression of CNK1 suppresses tumor cell growth and promotes apoptosis. As shown previously for apoptosis induced by Ki-Ras(G12V), CNK1-induced apoptosis is suppressed by a dominant inhibitor of the mammalian sterile 20 kinases 1 and (MST1/MST2). Immunoprecipitates of MST1 endogenous to LoVo colon cancer cells contain endogenous CNK1; however, no association of these two polypeptides can be detected in a yeast two-hybrid assay. CNK1 does, however, bind directly to the RASSF1A and RASSF1C polypeptides, constitutive binding partners of the MST1/2 kinases. Deletion of the MST1 carboxyl-terminal segment that mediates its binding to RASSF1A/C eliminates the association of MST1 with CNK1. Coexpression of CNK1 with the tumor suppressive isoform, RASSF1A, greatly augments CNK1-induced apoptosis, whereas the nonsuppressive RASSF1C isoform is without effect on CNK1-induced apoptosis. Overexpression of CNK1-(1-282), a fragment that binds RASSF1A but is not proapoptotic, blocks the apoptosis induced by CNK1 and by Ki-Ras(G12V). Thus, in addition to its positive role in the proliferative outputs of active Ras, the CNK1 scaffold protein, through its binding of a RASSF1A⅐MST complex, also participates in the proapoptotic signaling initiated by active Ras.CNK was discovered in a screen for modifiers of Ras-dependent photoreceptor development in Drosophila. CNK loss-offunction enhances the ability of a dominant-interfering allele of kinase suppressor of Ras to inhibit photoreceptor development and also suppresses the effects of activated alleles of Sevenless and Ras but not Raf (1). Conversely, overexpression of CNK greatly enhances the effect of Ras(G12V) on eye development but suppresses the effect of activated Raf. The latter phenomenon was attributed to sequestration of Raf, which binds directly to a carboxyl-terminal segment of CNK. On this basis, CNK was proposed to function as a positive element in Ras activation of Raf, and subsequent work established that CNK expression is required for Ras activation of Raf kinase in Drosophila S2 and mammalian cells (2, 3). Surprisingly, however, the ability of CNK to enhance Ras(G12V) action in eye development was shown to reside in a CNK aminoterminal fragment that lacks the ability to bind Raf and which does not alter Ras-induced mitogen-activated protein kinase activation (4). Moreover, this amino-terminal CNK fragment enhances the action of Ras(G12V,E37G), a Ras effector loop mutant that lacks the ability to activate Raf and mitogen-activated protein kinase (MAPK), whereas CNK does not cooperate with Ras(G12V,T35S), an effector loop mutant that retains the ability to signal via the Raf/MAPK pathway. These findings indicated that the rol...

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“…RASSF3 has a 60% amino acid homology to RASSF1A [68] and can be found in both normal and tumor cells [68]. It is the smallest member of the C-terminal RASSF family of proteins.…”

Section: Rassf3mentioning

confidence: 99%

RASSF tumor suppressor gene family: Biological functions and regulation

et al. 2014

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a b s t r a c tGenetic changes through allelic loss and nucleic acid or protein modifications are the main contributors to loss of function of tumor suppressor proteins. In particular, epigenetic silencing of genes by promoter hypermethylation is associated with increased tumor severity and poor survival. The RASSF (Ras association domain family) family of proteins consists of 10 members, many of which are tumor suppressor proteins that undergo loss of expression through promoter methylation in numerous types of cancers such as leukemia, melanoma, breast, prostate, neck, lung, brain, colorectal and kidney cancers. In addition to their tumor suppressor function, RASSF proteins act as scaffolding agents in microtubule stability, regulate mitotic cell division, modulate apoptosis, control cell migration and cell adhesion, and modulate NFjB activity and the duration of inflammation. The ubiquitous functions of these proteins highlight their importance in numerous physiological pathways. In this review, we will focus on the biological roles of the RASSF family members and their regulation.

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RASSF3 and NORE1: identification and cloning of two human homologues of the putative tumor suppressor gene RASSF1

Cited by 102 publications

References 36 publications

Nore1B regulates TCR signaling via Ras and Carma1

Nore1B regulates TCR signaling via Ras and Carma1

The Scaffold Protein CNK1 Interacts with the Tumor Suppressor RASSF1A and Augments RASSF1A-induced Cell Death

RASSF tumor suppressor gene family: Biological functions and regulation

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