Prenylated Rab acceptor domain family member 1 is involved in stimulated ACTH secretion and inhibition

Compton, Shannon; Kemppainen, Robert J.; Behrend, Ellen N.

doi:10.1016/j.cellsig.2009.08.007

Cited by 6 publications

(5 citation statements)

References 33 publications

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“…Members of the Prenylated Rab acceptor domain family (PRAF) are essential for the regulation of many cellular processes [22,23]. Here we have demonstrated that PRAF3 could induce apoptosis and inhibit migration and invasion of ESCC cells and hence may serve as a tumor suppressor in ESCC.…”

Section: Discussionmentioning

confidence: 97%

PRAF3 induces apoptosis and inhibits migration and invasion in human esophageal squamous cell carcinoma

et al. 2012

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BackgroundPrenylated Rab acceptor 1 domain family member 3 (PRAF3) is involved in the regulation of many cellular processes including apoptosis, migration and invasion. This study was conducted to investigate the effect of PRAF3 on apoptosis, migration and invasion in human esophageal squamous cell carcinoma (ESCC).MethodsThe expression of PRAF3 mRNA and protein in primary ESCC and the matched normal tissues (57cases) was determined by quantitative RT-PCR and Western blot. Immunohistochemical analysis of PRAF3 expression was carried out in paraffin-embedded sections of ESCC and correlated with clinical features. The role of PRAF3 in apoptosis, migration and invasion was studied in ESCC cell lines of Eca109 and TE-1 through the adenovirus mediated PRAF3 gene transfer. The effect of PRAF3 on apoptosis was analyzed by annexin V-FITC assay. The regulation of PRAF3 on migration was determined by transwell and wounding healing assay, while the cellular invasion was analyzed by matrigel-coated transwell assay.ResultsWe found that the expression of PRAF3 was significantly down-regulated in ESCC tissue compared with the matched normal tissue and was correlated with the clinical features of pathological grade, tumor stage and lymph node metastasis. Moreover, overexpression of PRAF3 induced cell apoptosis through both caspase-8 and caspase-9 dependent pathways, and inhibited cell migration and invasion by suppressing the activity of both MMP-2 and MMP-9 in human ESCC cell lines.ConclusionsOur data suggest that PRAF3 plays an important role in the regulation of tumor progression and metastasis and serves as a tumor suppressor in human ESCC. We propose that PRAF3 might be used as a potential therapeutic agent for human ESCC.

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Section: Discussionmentioning

confidence: 97%

PRAF3 induces apoptosis and inhibits migration and invasion in human esophageal squamous cell carcinoma

et al. 2012

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“…The idea that Rasd1 could influence hormone secretion is not new. A number of in vitro studies have reported inhibitory actions of Rasd1 on hormone secretion but the precise mechanisms mediating these inhibitory effects remains to be established [ 21 , 46 – 48 ]. It is established that high plasma osmolality results in the secretion and depletion of AVP in MCN cell bodies, even though mRNA expression of Avp is up-regulated in the PVN and SON [ 49 , 50 ].…”

Section: Discussionmentioning

confidence: 99%

“…In recent years many in vivo actions of DEX have been attributed to molecular signaling through Rasd1 [ 44 , 46 , 47 ] suggesting that DEX actions in the hypothalamus were the result of increased Rasd1 expression. Our in vivo observations of altered c-Fos and Nr4a1 expression by DEX treatment in the PVN and SON, where Rasd1 expression is elevated, prompted us to compare DEX treatment with Rasd1 overexpression on gene expression in mouse corticotroph AtT20 cells.…”

Section: Discussionmentioning

confidence: 99%

Rasd1, a small G protein with a big role in the hypothalamic response to neuronal activation

et al. 2016

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BackgroundRasd1 is a member of the Ras family of monomeric G proteins that was first identified as a dexamethasone inducible gene in the pituitary corticotroph cell line AtT20. Using microarrays we previously identified increased Rasd1 mRNA expression in the rat supraoptic nucleus (SON) and paraventricular nucleus (PVN) of the hypothalamus in response to increased plasma osmolality provoked by fluid deprivation and salt loading. RASD1 has been shown to inhibit adenylyl cyclase activity in vitro resulting in the inhibition of the cAMP-PKA-CREB signaling pathway. Therefore, we tested the hypothesis that RASD1 may inhibit cAMP stimulated gene expression in the brain.ResultsWe show that Rasd1 is expressed in vasopressin neurons of the PVN and SON, within which mRNA levels are induced by hyperosmotic cues. Dexamethasone treatment of AtT20 cells decreased forskolin stimulation of c-Fos, Nr4a1 and phosphorylated CREB expression, effects that were mimicked by overexpression of Rasd1, and inhibited by knockdown of Rasd1. These effects were dependent upon isoprenylation, as both farnesyltransferase inhibitor FTI-277 and CAAX box deletion prevented Rasd1 inhibition of cAMP-induced gene expression. Injection of lentiviral vector into rat SON expressing Rasd1 diminished, whereas CAAX mutant increased, cAMP inducible genes in response to osmotic stress.ConclusionsWe have identified two mechanisms of Rasd1 induction in the hypothalamus, one by elevated glucocorticoids in response to stress, and one in response to increased plasma osmolality resulting from osmotic stress. We propose that the abundance of RASD1 in vasopressin expressing neurons, based on its inhibitory actions on CREB phosphorylation, is an important mechanism for controlling the transcriptional responses to stressors in both the PVN and SON. These effects likely occur through modulation of cAMP-PKA-CREB signaling pathway in the brain.

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“…In fact, many of these studies associated PRAF1 and PRAF3 with several well-known cancer signaling pathways. For instance, PRAF1 (also known as Rabac1, PRA1, prenylin and Yip3), a Golgi complex, post-Golgi vesicle and endosomal transmembrane protein, was initially identified to interact with small GTPase proteins that regulate intracellular vesicle trafficking (8)(9)(10). In addition, PRAF1 has a crucial role in colorectal tumorigenesis by regulating the nuclear transport of β-catenin in TCF/β-catenin signaling (11).…”

Section: Praf2 Stimulates Cell Proliferation and Migration And Predicmentioning

confidence: 99%

PRAF2 stimulates cell proliferation and migration and predicts poor prognosis in neuroblastoma

Yco

Geerts

Koster

et al. 2013

International Journal of Oncology

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Prenylated Rab acceptor 1 domain family, member 2 (PRAF2) is a novel 19-kDa protein with four transmembrane-spanning domains that belongs to the PRAF protein family. Neuroblastoma (NB) is the most common malignant extracranial solid tumor of childhood that originates in primitive cells of the developing sympathetic nervous system. We investigated the correlation of PRAF2 mRNA expression to NB clinical and genetic parameters using Affymetrix expression analysis of a series of 88 NB tumors and examined the functional role of PRAF2 in an NB cell line using RNA interference. We found that high PRAF2 expression is significantly correlated to several unfavorable NB characteristics: MYCN amplification, high age at diagnosis, poor outcome and high INSS stage. The shRNA-mediated PRAF2 downregulation in the SK-N-SH NB cell line resulted in decreased cellular proliferation, migration and matrix-attachment. These findings were confirmed in NB patient tumor samples, where high PRAF2 expression is significantly correlated to bone and bone marrow metastasis, the main cause of death in NB patients. The present study shows that PRAF2 plays an essential role in NB tumorigenesis and metastasis.

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Prenylated Rab acceptor domain family member 1 is involved in stimulated ACTH secretion and inhibition

Cited by 6 publications

References 33 publications

PRAF3 induces apoptosis and inhibits migration and invasion in human esophageal squamous cell carcinoma

PRAF3 induces apoptosis and inhibits migration and invasion in human esophageal squamous cell carcinoma

Rasd1, a small G protein with a big role in the hypothalamic response to neuronal activation

PRAF2 stimulates cell proliferation and migration and predicts poor prognosis in neuroblastoma

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