Expression of the ornithine decarboxylase gene in response to asparagine in intestinal epithelial cells

1996 ◽  
Vol 271 (1) ◽  
pp. G164-G171 ◽  
Author(s):  
J. Y. Wang ◽  
M. J. Viar ◽  
P. M. Blanner ◽  
L. R. Johnson
Keyword(s):  
Ornithine Decarboxylase ◽  
Half Life ◽  
Cellular Protein ◽  
Mrna Levels ◽  
Intestinal Epithelial ◽  
Normal Rat ◽  
Fetal Bovine ◽  
Mucosal Growth ◽  
Rate Limiting ◽  
In Cells

Refeeding fasted rats significantly stimulates mucosal growth and ornithine decarboxylase (ODC), the rate-limiting enzyme in the biosynthesis of polyamines, but the exact mechanism responsible for induction of ODC at the molecular level is unknown. Of normal dietary constituents, the amino acid asparagine markedly increases ODC activity and mucosal growth when administered intragastrically. The current study examined the expression of the ODC gene in IEC-6 cells (a line of normal rat small intestinal crypt cells) after exposure to asparagine. Cells were grown in Dulbecco's minimal essential medium containing 5% dialyzed fetal bovine serum. They were deprived of serum for 24 h before experiments. Exposure to asparagine at the dose of 10 mM resulted in the rapid increase in ODC mRNA levels. The increased expression of the ODC gene began 1 h after and peaked between 3 and 5 h after treatment with asparagine. Maximum increases in ODC mRNA levels were approximately fivefold the normal value. Increased levels of ODC mRNA in cells exposed to asparagine were paralleled by increases in ODC protein and enzyme activity and cellular polyamine levels. The half-life of mRNA for ODC in unstimulated IEC-6 cells was approximately 30 min and increased to > 2 h in cells exposed to 10 mM asparagine. The half-life of ODC activity also was increased in asparagine-treated cells. When cellular protein synthesis was inhibited by cycloheximide, asparagine superinduced ODC mRNA levels. Furthermore, asparagine also significantly stimulated DNA synthesis in IEC-6 cells. These results indicate that 1) asparagine stimulates ODC in IEC-6 cells through multiple pathways and 2) increased ODC mRNA levels result partly from a delay in the rate of degradation. These findings suggest that luminal amino acids stimulate gut mucosal growth in association with their ability to regulate ODC gene expression.

Synergistic induction of ornithine decarboxylase by asparagine and gut peptides in intestinal crypt cells

1998 ◽  
Vol 274 (6) ◽  
pp. C1476-C1484 ◽  
Author(s):  
Jian-Ying Wang ◽  
Ji Li ◽  
Anami R. Patel ◽  
Stephen Summers ◽  
Li Li ◽  
...  
Keyword(s):  
Ornithine Decarboxylase ◽  
Half Life ◽  
Mrna Levels ◽  
Gut Peptides ◽  
Intestinal Crypt ◽  
Simultaneous Addition ◽  
Protein Levels ◽  
Synergistic Induction ◽  
Crypt Cells ◽  
In Cells

The objective of this study was to determine whether the amino acid asparagine stimulated the activity of ornithine decarboxylase (ODC) synergistically with epidermal growth factor (EGF) or gastrin in IEC-6 cells, a line of normal rat small intestinal crypt cells. Cells were grown in DMEM containing 5% dialyzed fetal bovine serum, and serum was deprived for 24 h before experiments. Exposure to EGF or gastrin alone increased ODC activity 4.5- to 6-fold. Asparagine alone increased the enzyme activity 10- to 13-fold in IEC-6 cells. Simultaneous addition of asparagine and EGF or gastrin, however, increased ODC activity more than 40-fold. In contrast, there was no synergistic induction of ODC activity when gastrin and EGF were added together. Increased ODC activity in cells treated with asparagine and EGF or gastrin was associated with an increase in ODC mRNA and protein levels. The rate of transcription of the ODC gene was significantly increased by exposure to EGF or gastrin. Asparagine alone had little or no effect on the rate of transcription of the ODC gene. When given together with EGF or gastrin, asparagine also had no additional effect on the transcription rate of the ODC gene. The half-life of mRNA for ODC in unstimulated IEC-6 cells was ∼30 min and increased to more than 2 h in cells exposed to asparagine, although neither gastrin nor EGF prolonged the stability of ODC mRNA. The half-life of mRNA for ODC after combined addition of asparagine and EGF or gastrin was extended to ∼2 h, similar to asparagine alone. Combined addition of asparagine and EGF or gastrin also significantly increased DNA synthesis compared with cells exposed to each of the three agents alone. In conclusion, 1) simultaneous addition of asparagine and EGF or gastrin increases ODC activity in a synergistic manner and 2) asparagine increases ODC mRNA levels through completely distinct mechanisms from EGF or gastrin. EGF or gastrin specifically stimulates transcription of the ODC gene, whereas asparagine affects a posttranscriptional process.

Intestinal ornithine decarboxylase: half-life and regulation by putrescine

1990 ◽  
Vol 258 (2) ◽  
pp. G308-G315 ◽  
Author(s):  
K. Iwami ◽  
J. Y. Wang ◽  
R. Jain ◽  
S. McCormack ◽  
L. R. Johnson
Keyword(s):  
Ornithine Decarboxylase ◽  
Intestinal Mucosa ◽  
Half Life ◽  
Time Course ◽  
Polyamine Synthesis ◽  
Mammalian Tissues ◽  
Growth Promoting ◽  
Mucosal Growth ◽  
Rate Limiting ◽  
Intestinal Crypt Cell

Ornithine decarboxylase (ODC) is the primary rate-limiting enzyme for polyamine synthesis. ODC levels are increased in most tissues, including the intestinal mucosa, by growth-promoting agents. This enzyme has a brief half-life of from 5 to 30 min in mammalian tissues and is regulated by its product; putrescine. The current study examines the turnover and regulation of ODC in the mucosa of the small intestine. With the use of scraped intestinal mucosa from cycloeximide-treated rats, the time course of the decline in ODC activity yielded a half-life of approximately 22 min. Labeling enzyme protein with [3H]difluoromethylornithine (DFMO) resulted in a nearly identical estimation of half-life. ODC activity of mucosa from isolated gut segments stimulated by luminal glycine (0.1-0.4 M) was enhanced 60-100% by 10 mM putrescine administered luminally. Putrescine alone had no effect on ODC. In contrast, 10(-7) M putrescine prevented 80% of the ODC activity stimulated by asparagine in IEC-6 cells (a rat intestinal crypt cell line). The half-life of ODC in unstimulated IEC-6 cells was 20 min and increased to 35 min in cells exposed to 10 mM asparagine. These data demonstrate that ODC of nonproliferating villous cells is regulated differently from the identical enzyme in proliferating crypt cells. Therefore, conclusions regarding mucosal growth should not be based totally on ODC activity from whole mucosa, since it is essentially a measure of only the enzyme present in the villous cells.

scholarly journals Inhibition of polyamine synthesis induces p53 gene expression but not apoptosis

1999 ◽  
Vol 276 (4) ◽  
pp. C946-C954 ◽  
Author(s):  
Li Li ◽  
Ji Li ◽  
Jaladanki N. Rao ◽  
Minglin Li ◽  
Barbara L. Bass ◽  
...  
Keyword(s):  
Gene Expression ◽  
Growth Inhibition ◽  
P53 Protein ◽  
Specific Inhibitor ◽  
P53 Gene ◽  
Mrna Levels ◽  
Intestinal Epithelial ◽  
Polyamine Biosynthesis ◽  
Fetal Bovine ◽  
P53 Mrna

The nuclear phosphoprotein p53 acts as a transcription factor and is involved in growth inhibition and apoptosis. The present study was designed to examine the effect of decreasing cellular polyamines on p53 gene expression and apoptosis in small intestinal epithelial (IEC-6) cells. Cells were grown in DMEM containing 5% dialyzed fetal bovine serum in the presence or absence of α-difluoromethylornithine (DFMO), a specific inhibitor of polyamine biosynthesis, for 4, 6, and 12 days. The cellular polyamines putrescine, spermidine, and spermine in DFMO-treated cells decreased dramatically at 4 days and remained depleted thereafter. Polyamine depletion by DFMO was accompanied by a significant increase in expression of the p53 gene. The p53 mRNA levels increased 4 days after exposure to DFMO, and the maximum increases occurred at 6 and 12 days after exposure. Increased levels of p53 mRNA in DFMO-treated cells were paralleled by increases in p53 protein. Polyamines given together with DFMO completely prevented increased expression of the p53 gene. Increased expression of the p53 gene in DFMO-treated cells was associated with a significant increase in G1 phase growth arrest. In contrast, no features of programmmed cell death were identified after polyamine depletion: no internucleosomal DNA fragmentation was observed, and no morphological features of apoptosis were evident in cells exposed to DFMO for 4, 6, and 12 days. These results indicate that 1) decreasing cellular polyamines increases expression of the p53 gene and 2) activation of p53 gene expression after polyamine depletion does not induce apoptosis in intestinal crypt cells. These findings suggest that increased expression of the p53 gene may play an important role in growth inhibition caused by polyamine depletion.

Gastrin stimulates expression of protooncogene c-myc through a process involving polyamines in IEC-6 cells

1995 ◽  
Vol 269 (6) ◽  
pp. C1474-C1481 ◽  
Author(s):  
J. Y. Wang ◽  
H. Wang ◽  
L. R. Johnson
Keyword(s):  
Specific Inhibitor ◽  
Cellular Protein ◽  
Mucosal Cell ◽  
Mrna Levels ◽  
Maximum Increase ◽  
Polyamine Biosynthesis ◽  
Small Intestinal ◽  
Rate Limiting ◽  
Mucosal Cell Proliferation ◽  
Rapid Appearance

The current study tested the hypothesis that the protooncogene c-myc is involved in the mechanism by which gastrin modulates mucosal cell proliferation. Studies were conducted in the IEC-6 cell line, derived from rat small intestinal crypt cells. Administration of gastrin resulted in the rapid appearance of c-myc mRNA in IEC-6 cells. The increased expression of c-myc began 1 h and peaked 4 h after exposure to gastrin. Maximum increase in c-myc mRNA levels was 7.5-fold the normal value. When cellular protein synthesis was inhibited by addition of cycloheximide, gastrin superinduced c-myc mRNA levels. Gastrin also significantly increased the mRNA levels for ornithine decarboxylase (ODC), the rate-limiting enzyme for polyamine biosynthesis, enzyme activity, and intracellular polyamines in IEC-6 cells. Treatment with alpha-difluoromethylornithine (DFMO), a specific inhibitor of ODC, not only completely depleted intracellular polyamines but also significantly prevented the increased expression of c-myc in cells exposed to gastrin. These results show that 1) gastrin stimulates both polyamine biosynthesis and the expression of the c-myc protooncogene, and 2) depletion of intracellular polyamines by DFMO significantly prevented the increased expression of c-myc by gastrin.

Glucocorticoids induce a near-total suppression of hyaluronan synthase mRNA in dermal fibroblasts and in osteoblasts: a molecular mechanism contributing to organ atrophy

2000 ◽  
Vol 349 (1) ◽  
pp. 91-97 ◽  
Author(s):  
Wei ZHANG ◽  
Catherine E. WATSON ◽  
Connie LIU ◽  
Kevin Jon WILLIAMS ◽  
Victoria P. WERTH
Keyword(s):  
Gene Transcription ◽  
Half Life ◽  
Time Course ◽  
Molecular Mechanisms ◽  
Dermal Fibroblasts ◽  
Steroid Hormone Receptors ◽  
Hyaluronan Synthase ◽  
Osteosarcoma Cell ◽  
Mrna Levels ◽  
In Cells

Glucocorticoid (GC) administration induces atrophy of skin, bone, and other organs, partly by reducing tissue content of glycosaminoglycans, particularly hyaluronic acid (HA). We took advantage of the recent cloning of the three human hyaluronan synthase (HAS) enzymes (HAS1, HAS2 and HAS3), to explore the molecular mechanisms of this side effect. Northern and slot blots performed on RNA extracted from cultured dermal fibroblasts and the MG-63 osteoblast-like osteosarcoma cell line indicated that HAS2 is the predominant HAS mRNA in these cells. Incubation of both cell types for 24 h in the presence of 10-6 M dexamethasone (DEX) resulted in a striking 97-98% suppression of HAS2 mRNA levels. Time-course studies in fibroblasts demonstrated suppression of HAS2 mRNA to 28% of control by 1 h, and to 1.2% of control by 2 h, after addition of DEX. Dose-response studies in fibroblasts indicated that the majority of the suppressive effect required concentrations characteristic of cell-surface GC receptors, a point confirmed by persistent DEX-induced suppression in the presence of RU486, an antagonist of classic cytosolic steroid hormone receptors. Nuclear run-off experiments showed a 70% suppression of HAS2 gene transcription in nuclei from DEX-treated fibroblasts, which is unlikely to fully explain the rapid 50-80-fold reduction in message levels. Experiments with actinomycin D (AMD) demonstrated that the message half-life was 25 min in cells without DEX, whereas the combination of AMD with DEX dramatically increased the half-life of HAS2 mRNA, suggesting that DEX acts by inducing a short-lived destabilizer of the HAS2 message. Direct assessment of HAS2 mRNA stability by wash-out of incorporated uridine label established a half-life of 31 min in cells without DEX, which substantially shortened in the presence of DEX. In conclusion, GCs induce a rapid and sustained, near-total suppression of HAS2 message levels, mediated through substantial decreases in both gene transcription and message stability. These effects may contribute to the loss of HA in GC-treated organs.

scholarly journals A Novel Role of PM Extracts on the Post-Transcriptional Control of Pro-Inflammatory Mediators, IL-6 and CXCL8

Atmosphere ◽  
2019 ◽  
Vol 10 (5) ◽  
pp. 270
Author(s):  
Evasomary Rivera-Ramírez ◽  
Loyda B. Méndez ◽  
Andrea Ortíz-Rivera ◽  
Rosa I. Rodríguez-Cotto ◽  
Braulio Jiménez-Vélez
Keyword(s):  
Steady State ◽  
Inflammatory Mediators ◽  
Half Life ◽  
Transcriptional Control ◽  
Mrna Levels ◽  
Organic Extracts ◽  
Steady State Levels ◽  
Mrna Half Life ◽  
Cxcl8 Mrna ◽  
In Cells

Exposure to airborne particulate matter (PM) has been associated with the transcriptional up-regulation of pro-inflammatory mediators. However, the effect of PM on post-transcriptional regulation of pro-inflammatory mediators has not been fully explored. In this study, we examined the acute effect of organic extracts from urban PM, rural PM and diesel exhaust particles (DEP) on the post-transcriptional control of interleukin-6 (IL-6) and interleukin-8 (CXCL8) using a human bronchial epithelial cell line. Both PM and DEP extracts induced the release of IL-6 and CXCL8 after 24 h of exposure. Time-course experiments were conducted to examine changes in mRNA steady-state levels and half-lives. The steady-state levels of CXCL8 mRNA increase at 15 min on cells exposed to both PM and DEP extracts. Meanwhile only the urban extract induced significant increases of IL-6 mRNA levels at 15 min. Indirect measurements of IL-6 mRNA half-life showed a dramatic increase in cells exposed to the organic extracts. CXCL8 mRNA half-life increases in cells exposed to PM extracts and not DEP extract. Nuclear run-ons demonstrated that the urban PM and DEP extracts promoted an up-regulation in the transcription rate of CXCL8 at 15 min but not for IL-6. Urban and rural PM influences the post-transcriptional control of CXCL8.

Regulation of mRNA Stability by Heat Shock Cognate Protein 70 (Hsc70) under the Control of Cytokines.

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 36-36 ◽  
Author(s):  
Hirotaka Matsui ◽  
Toshiya Inaba
Keyword(s):  
Atpase Activity ◽  
Mrna Stability ◽  
Protein Complex ◽  
Half Life ◽  
Rna Binding ◽  
Biological Significance ◽  
Binding Potential ◽  
Mrna Levels ◽  
Cells Cultured ◽  
In Cells

Abstract Downstream pathways of cytokines promoting cell division and survival have long been a focus of intensive research. p27KIP1, a cyclin-dependent kinase inhibitor, and Bim, a BH3-only cell death activator, are downregulated by cytokines and are known to be key factors in mechanisms of cytokine-induced growth and survival. In murine IL-3-dependent Baf-3 cells, Bim and p27 are regulated by IL-3 at the mRNA levels. To test whether Bim is transcriptionally regulated, we identified cis -regulating elements of Bim gene in Baf-3 cells, but none of them are under the control of IL-3. Then we tested a possibility that mRNA stability is controlled by IL-3. β-globin mRNA enforcedly expressed in Baf-3 cells were stable either in the presence or absence of IL-3. When its 3′ untranslated region (3′UTR) was replaced by that of Bim mRNA, stability of the fusion message was impaired in cells cultured in the presence of IL-3, but not in the absence of IL-3. Then we measured mRNA half-life in cytosol (S100 extract). Radiolabeled Bim mRNA with the 5′ cap and a poly(A) tail of 100 residues synthesized in vitro was stable in cytosol from Baf-3 cells cultured in the absence of IL-3 (half-life: 30 min), but was degraded quickly in the presence of IL-3 (half-life: less than 10 min). By contrast, cap-/poly(A)- mRNA was unstable in cytosol from cells cultured with or without IL-3. The half-life of p27 mRNA was also elongated by IL-3 starvation, while the stability of c-fos mRNA was not changed. Condensation of proteins bound to mRNA using RNA-affinity chromatography revealed that a protein of around 75 KDa bound to the 3′UTR of Bim and p27 mRNA (but not c-fos mRNA) more avidly in cells cultured without IL-3 than in cells with IL-3. Mass spectrometry and immunoblot analysis identified this protein to be Hsc70. Hsc70 was reported to bind to AU-rich RNA sequences such as AUUUA avidly, but its biological significance was not known. We found that Hsc70 acts as an mRNA stabilizing factor by immunodepletion study. Because the protein expression level of Hsc70 in Baf-3 cells was not increased by IL-3 starvation, IL-3 likely inhibits RNA-binding potential of Hsc70. To obtain insights into its mechanism, we measured ATPase activity of Hsc70 protein complex. We found that the complex formed in Baf-3 cells cultured in the presence of IL-3 has high ATPase activity (i.e., Hsc70 forms ATP-bound form preferentially), while that in the absence of IL-3 is no more than background levels (i.e., Hsc70 forms ADP-bound form), raising a possibility that the binding potential to Bim mRNA and ATP/ADP-bound status of Hsc70 is related. Since cochaperones bind to Hsc70 and regulate its ATPase activity, we tested their expression and binding capacity to Hsc70. We found that IL-3 upregulates the expression of Bag-4 (also SODD) and the potential of CHIP to bind to Hsc70 (these two cochaperones are known to induce Hsc70 to ATP-bound form). Moreover, IL-3 downregulates the potential of HIP and Hsp40 to bind to Hsc70 (they are known to induce to ADP-bound form). Subsequently, Hsc70 protein complex is considered to form the ATP-bound status and has less binding ability to Bim mRNA. This novel gene-specific mechanism for the regulation of mRNA stability by the chaperone/cochaperone complex may play important roles in hematopoiesis.

scholarly journals Metabolism of polyamines by cultured glioma cells. Effect of asparagine on γ-aminobutyric acid concentrations

1980 ◽  
Vol 188 (2) ◽  
pp. 387-392 ◽  
Author(s):  
U Bachrach
Keyword(s):  
Ornithine Decarboxylase ◽  
Half Life ◽  
Diamine Oxidase ◽  
Glucose Solution ◽  
Glioma Cells ◽  
Aminobutyric Acid ◽  
Complete Medium ◽  
Gamma Aminobutyric Acid ◽  
Kinetics Of ◽  
In Cells

The activity of ornithine decarboxylase (EC 4.1.1.17) increased in confluent cultures of glioma C6BU-1 cells 3 h after adding a complete serum-containing medium, and was maximal 5 h later. The activity of S-adenoxyl-L-methionine decarboxylase (EC 4.1.1.50) increased soon after addition of the complete medium to the cells, and reached its peak after 11 h. The activity of diamine oxidase (EC 1.4.3.6) also increased soon after adding complete medium and was maximal 8h later, when the activity of ornithine decarboxylase reached its peak. The increase in the activity of S-adenosyl-L-methionine decarboxylase was accompanied by changes in cellular spermidine and spermine concentrations, whereas the increase in the activity of diamine oxidase was followed by the accumulation of gamma-aminobutyric acid, which was detected both in the cells and in the medium. Asparagine enhanced the utilization of radioactive putrescine by glioma cells suspended in buffered-salt/glucose solution and increased intracellular and extracellular gamma-aminobutyric acid concentrations. Radioactive putrescine was converted into spermidine and spermine by glioma cells after addition of a serum-containing medium, but not after adding buffered–salt/glucose solutions, in the presence or absence of asparagine. The kinetics of ornithine decarboxylase ‘induction’ and the half-life of the enzyme differed in cells incubated with buffered asparagine solutions and serum-containing media.

Multiple pathways for the regulation of ornithine decarboxylase in intestinal epithelial cells

1990 ◽  
Vol 258 (3) ◽  
pp. G454-G460 ◽  
Author(s):  
D. D. Ginty ◽  
M. Marlowe ◽  
P. H. Pekala ◽  
E. R. Seidel
Keyword(s):  
Epithelial Cells ◽  
Enzymatic Activity ◽  
Ornithine Decarboxylase ◽  
Specific Activity ◽  
Intestinal Epithelial Cells ◽  
Mrna Levels ◽  
Dependent Manner ◽  
Intestinal Epithelial ◽  
Mrna Accumulation ◽  
Calmodulin Antagonist

The regulation of ornithine decarboxylase (ODC) was examined in an intestinal epithelial crypt cell line (IEC-6). Addition of fetal bovine serum or growth factors to quiescent preconfluent cells resulted in a 20- to 30-fold increase in the specific activity of ODC, which was maximal at approximately 4 h. In contrast, ODC mRNA levels either did not change or increased only twofold over the time period examined. The increased enzymatic activity was blocked by cycloheximide, putrescine, and the calmodulin antagonist N-(6-aminohexyl)-5-chloro-1-napthalinesulfonamide (W-7). Cycloheximide alone increased mRNA levels and potentiated the induction in response to serum, suggesting that protein synthesis is not required for the increase in mRNA accumulation. In contrast to its effect on ODC activity, W-7 was without effect on the serum-stimulated increase in ODC or c-fos mRNA levels. Putrescine decreased ODC activity, but not mRNA content, in a dose-dependent manner with an IC50 between 0.1 and 1.0 microM. Also, serum stimulation resulted in a threefold increase in the stability of the enzyme in the presence of cycloheximide; this effect was blocked by pretreatment with W-7. Enzymatic activity was paralleled by ODC protein content as determined by [3H] difluoromethylornithine binding. Finally, the induction of enzyme activity was due entirely to an increase in Vmax as no detectable change in Km for ornithine was detected. These results suggest that ODC is regulated at multiple levels by independent signaling pathways in cultured intestinal epithelial cells. Increased levels of active ODC protein and enzymatic activity are sensitive to W-7 and putrescine.(ABSTRACT TRUNCATED AT 250 WORDS)

scholarly journals Competition between RNA-binding proteins CELF1 and HuR modulates MYC translation and intestinal epithelium renewal

2015 ◽  
Vol 26 (10) ◽  
pp. 1797-1810 ◽  
Author(s):  
Lan Liu ◽  
Miao Ouyang ◽  
Jaladanki N. Rao ◽  
Tongtong Zou ◽  
Lan Xiao ◽  
...  
Keyword(s):  
Intestinal Epithelium ◽  
Rna Binding ◽  
Rna Binding Proteins ◽  
Binding Protein ◽  
The Body ◽  
Small Intestinal Mucosa ◽  
Mrna Levels ◽  
Intestinal Epithelial ◽  
Mucosal Growth ◽  
The Stability

The mammalian intestinal epithelium is one of the most rapidly self-renewing tissues in the body, and its integrity is preserved through strict regulation. The RNA-binding protein (RBP) ELAV-like family member 1 (CELF1), also referred to as CUG-binding protein 1 (CUGBP1), regulates the stability and translation of target mRNAs and is implicated in many aspects of cellular physiology. We show that CELF1 competes with the RBP HuR to modulate MYC translation and regulates intestinal epithelial homeostasis. Growth inhibition of the small intestinal mucosa by fasting in mice was associated with increased CELF1/ Myc mRNA association and decreased MYC expression. At the molecular level, CELF1 was found to bind the 3′-untranslated region (UTR) of Myc mRNA and repressed MYC translation without affecting total Myc mRNA levels. HuR interacted with the same Myc 3′-UTR element, and increasing the levels of HuR decreased CELF1 binding to Myc mRNA. In contrast, increasing the concentrations of CELF1 inhibited formation of the [HuR/ Myc mRNA] complex. Depletion of cellular polyamines also increased CELF1 and enhanced CELF1 association with Myc mRNA, thus suppressing MYC translation. Moreover, ectopic CELF1 overexpression caused G1-phase growth arrest, whereas CELF1 silencing promoted cell proliferation. These results indicate that CELF1 represses MYC translation by decreasing Myc mRNA association with HuR and provide new insight into the molecular functions of RBPs in the regulation of intestinal mucosal growth.

Sign in / Sign up

Export Citation Format

Share Document