Regulation of Mucin Gene Expression by CREB via a Nonclassical Retinoic Acid Signaling Pathway

Kim, Seung Wook; Hong, Joon Seok; Ryu, Seung-Hee; Chung, Won Jee; Yoon, Joo Heon; Koo, Ja Seok

doi:10.1128/mcb.02385-06

Cited by 58 publications

(59 citation statements)

References 75 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…We observed maximal reduction of endogenous RAR/RXR protein 72 h after transfection. Successful suppression of RAR/RXR has been demonstrated previously and residual RAR/RXR were not sufficient enough to transmit RA signaling [13,14]. Likewise, the RA-induced expressions of CREB mRNA and protein were not significantly reduced after co-transfection with a combination of RAR and RXR siRNAs ( Figure 2, C and D), strongly indicating that RAR and RXR receptors are not involved in RA-induced CREB regulation.…”

Section: Ra-induced Upregulation Of Creb Is Independent Of Retinoic Asupporting

confidence: 55%

“…Our previous studies showed that RA-activated CREB plays a critical role in the expression of mucin genes, which are typical indicators of bronchial mucous cell differentiation [13,14]. We also observed that CREB expression is very low in fully differentiated metaplastic squamous bronchial epithelial cells.…”

Section: Introductionmentioning

confidence: 51%

“…It has been well documented that the physiological effects of RAs are mediated through two families of nuclear receptors (NRs), the RA receptor (RAR) and the retinoid X receptor (RXR), which control transcription initiation by binding to RA-response elements (RAREs) [1,11,12]. However, we recently demonstrated that RA rapidly activates CREB without using RAR/RXR in normal human tracheobronchial epithelial (NHTBE) cells [13,14].…”

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Sp1 up-regulates cAMP-response-element-binding protein expression during retinoic acid-induced mucous differentiation of normal human bronchial epithelial cells

Hong

Kim

Koo

2008

Biochemical Journal

Self Cite

View full text Add to dashboard Cite

Cyclic 3′,5′-adenosine monophosphate (cAMP) response-element (CRE) binding protein (CREB) is an important transcription factor that is differentially regulated in cells of various types. We recently reported that RA rapidly activates CREB without using retinoic acid (RA) receptors RAR and RXR in normal human tracheobronchial epithelial (NHTBE) cells. However, little is known about RA's role in the physiologic regulation of CREB expression in the early mucous differentiation of NHTBE cells. Here, we report that RA upregulated CREB gene expression and that using 5′-serial deletion promoter analysis and mutagenesis analyses, two Sp1-binding sites located at nucleotides −217 and −150, which flank the transcription initiation site, were essential for RA induction of CREB gene transcription. Furthermore, we found that CREs located at nucleotides −119 and −98 contributed to basal promoter activity. Interestingly, RA also upregulated Sp1 in a time-and dose-dependent manner. Knockdown of endogenous Sp1 using small interfering RNA (siRNA) decreased RA-induced CREB gene expression. However, the converse was not true: knockdown of CREB using CREB siRNA did not affect RA-induced Sp1 gene expression. We conclude that RA upregulates CREB gene expression during the early stage of NHTBE cell differentiation and that RA-inducible Sp1 plays a major role in upregulating human CREB gene expression. This result implies that cooperation of these two transcription factors play a crucial role in mediating early events of normal mucous cell differentiation of bronchial epithelial cells.

show abstract

Section: Ra-induced Upregulation Of Creb Is Independent Of Retinoic Asupporting

confidence: 55%

Section: Introductionmentioning

confidence: 51%

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Sp1 up-regulates cAMP-response-element-binding protein expression during retinoic acid-induced mucous differentiation of normal human bronchial epithelial cells

Hong

Kim

Koo

2008

Biochemical Journal

Self Cite

View full text Add to dashboard Cite

show abstract

“…It has been suggested that CREB may play a key role in early neural development. Previous data have shown that CREB phosphorylation is induced through different mechanisms in different types of cells during RA-mediated differentiation (Kim et al, 2007). Therefore, we investigated the roles of CREB in mediating differentiation induced by RA in ES cells.…”

Section: Discussionmentioning

confidence: 95%

pCREB is Involved in Neural Induction of Mouse Embryonic Stem Cells by RA

Shan

Shen

et al. 2008

The Anatomical Record

View full text Add to dashboard Cite

Mouse embryonic stem (ES) cells can be induced by various chemicals to differentiate into a variety of cell types in vitro. In our study, retinoic acid (RA), one of the most important inducers, used at a concentration of 5 mM, was found to induce the differentiation of ES cells into neural progenitor cells (NPCs). During embryoid body (EB) differentiation, the level of active cyclic AMP response element-binding protein (CREB) was relatively high when 5 mM RA treatment was performed. Inhibition of CREB activity committed EBs to becoming other germ layers, whereas increased expression of CREB enhanced NPC differentiation. Moreover, RA increased the expression of active CREB by enhancing the activity of JNK. Our research suggests that CREB plays a role in RA-induced NPC differentiation by increasing the expression of active JNK. Anat Rec,

show abstract

“…However, certain rapid retinoid responses, such as activation of GTPase Rac (21), protein kinase C (22), and ERK2 (23), and phosphorylation of cAMP-response element-binding protein (24,25), cannot be explained by classic transcriptional regulation. Thus, subcellular localization of retinoid receptors changes during development of the testes (26) and during various stages of the menstrual cycle (27).…”

mentioning

confidence: 99%

A Unique Cytoplasmic Localization of Retinoic Acid Receptor-γ and Its Regulations

Han

Zhou

Kim

et al. 2009

Journal of Biological Chemistry

View full text Add to dashboard Cite

Recent evidence suggests that extranuclear action of retinoid receptors is involved in mediating the pleiotropic effects of retinoids. However, whether they reside in the cytoplasm remains elusive. Here, we showed that retinoic acid receptor-␥ (RAR␥) was cytoplasmic in confluent cells, or when cells were released from serum depletion or treated with growth factors. In studying the regulation of RAR␥ subcellular localization, we observed that ectopically overexpressed RAR␥ was mainly cytoplasmic irrespective of serum concentration and cell density. The cytoplasmic retention of RAR␥ was inhibited by ligand retinoic acid (RA). In addition, coexpression of retinoid X receptor-␣ (RXR␣) resulted in nuclear localization of RAR␥ through their heterodimerization. Mutagenesis studies revealed that a C-terminal fragment of RXR␣ potently prevents RA-induced RAR␥ nuclear localization and transcriptional function. Furthermore, our results showed that the cytoplasmic retention of RAR␥ was due to the presence of its unique N-terminal A/B domain, which was subject to regulation by p38 MAPK-mediated phosphorylation. Deletion or mutation of the N-terminal A/B domain largely impaired its cytoplasmic localization. Together, our data demonstrate that the subcellular localization of RAR␥ is regulated by complex interactions among ligand binding, receptor phosphorylation, and receptor dimerizations.

show abstract

Regulation of Mucin Gene Expression by CREB via a Nonclassical Retinoic Acid Signaling Pathway

Cited by 58 publications

References 75 publications

Sp1 up-regulates cAMP-response-element-binding protein expression during retinoic acid-induced mucous differentiation of normal human bronchial epithelial cells

Sp1 up-regulates cAMP-response-element-binding protein expression during retinoic acid-induced mucous differentiation of normal human bronchial epithelial cells

pCREB is Involved in Neural Induction of Mouse Embryonic Stem Cells by RA

A Unique Cytoplasmic Localization of Retinoic Acid Receptor-γ and Its Regulations

Contact Info

Product

Resources

About