Oct-1 functions as a sensor for metabolic and stress signals

Wang, Peixiang; Jin, Tianru

doi:10.4161/isl.2.1.10017

Cited by 16 publications

(11 citation statements)

References 16 publications

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“…Moreover, recent evidences suggest that Oct-1 may play a role in metabolic homeostasis by acting as a sensor for cAMP (cyclic AMP). In particular, elevation of cAMP in pancreatic and intestinal endocrine cells reduces nuclear Oct-1 content [39], [40], and this is consistent with previous observations indicating that expression of HMGA1 increases in response to cAMP [12], [41], thus suggesting that increased HMGA1 expression could be due, at least in part, to the reduction of Oct-1 content.…”

Section: Discussionsupporting

confidence: 91%

Transcriptional Regulation of the HMGA1 Gene by Octamer-Binding Proteins Oct-1 and Oct-2

et al. 2013

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The High-Mobility Group AT-Hook 1 (HMGA1) protein is an architectural transcription factor that binds to AT-rich sequences in the promoter region of DNA and functions as a specific cofactor for gene activation. Previously, we demonstrated that HMGA1 is a key regulator of the insulin receptor (INSR) gene and an important downstream target of the INSR signaling cascade. Moreover, from a pathogenic point of view, overexpression of HMGA1 has been associated with human cancer, whereas functional variants of the HMGA1 gene have been recently linked to type 2 diabetes mellitus and metabolic syndrome. However, despite of this biological and pathological relevance, the mechanisms that control HMGA1 gene expression remain unknown. In this study, to define the molecular mechanism(s) that regulate HMGA1 gene expression, the HMGA1 gene promoter was investigated by transient transfection of different cell lines, either before or after DNA and siRNA cotransfections. An octamer motif was identified as an important element of transcriptional regulation of this gene, the interaction of which with the octamer transcription factors Oct-1 and Oct-2 is crucial in modulating HMGA1 gene and protein expression. Additionally, we demonstrate that HMGA1 binds its own promoter and contributes to its transactivation by Oct-2 (but not Oct-1), supporting its role in an auto-regulatory circuit. Overall, our results provide insight into the transcriptional regulation of the HMGA1 gene, revealing a differential control exerted by both Oct-1 and Oct-2. Furthermore, they consistently support the hypothesis that a putative defect in Oct-1 and/or Oct-2, by affecting HMGA1 expression, may cause INSR dysfunction, leading to defects of the INSR signaling pathway.

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Section: Discussionsupporting

confidence: 91%

Transcriptional Regulation of the HMGA1 Gene by Octamer-Binding Proteins Oct-1 and Oct-2

et al. 2013

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“…The ALDH1A1 promoter has binding sites for the AP-1 (17) and Oct-1 (18) transcription factors. Oct-1 is stabilized and translocated into the nucleus due to radiation, ROS (19) and HPV16 infection (20). The low expression of ALDH1A1 has also been recognized in the normal tonsillar squamous epithelium (21).…”

Section: Discussionmentioning

confidence: 99%

Expression of ALDH1A1 and CD44 in primary head and neck squamous cell carcinoma and their value for carcinogenesis, tumor progression and cancer stem cell identification

et al. 2015

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Abstract. In head and neck squamous cell carcinoma (HNSCC), aldehyde dehydrogenase 1 family, member A1 (ALDH1A1) and hyaluronan receptor cluster of differentiation 44 (CD44) are often used as cancer stem cell (CSC) markers. The aim of the present study was to examine the relevance of these proteins for HNSCC in general and for the identification of CSCs. Tumors from 48 patients with primary HNSCC were analyzed for the expression of ALDH1A1 and CD44. Additionally, the association of the proteins with the proliferation rate and epidermal growth factor receptor (EGFR) expression was analyzed. ALDH1A1 was expressed in 54.2% of the carcinoma samples while CD44 was expressed in 89.6% of the carcinoma samples. Most notably, these proteins were often not expressed exclusively in a subpopulation, but also in the majority of tumor cells (ALDH1A1: 30.8% of ALDH1A1 + tumors; CD44: 65.1% of CD44 + tumors). Furthermore, patients with ALDH1A1 + tumors exhibited worse survival rates. CD44 and EGFR expression patterns were overlapping within the tumors and the expression rates were significantly connected. Ki-67 + tumor cells often expressed CD44. ALDH1A1 and CD44 expression patterns only partly overlapped. Consequently, ALDH1A1 and CD44 play significant roles in carcinogenesis and tumor progression. Within the present study, CD44 appeared to interact with EGFR and was more often expressed in primary HNSCC than the marker ALDH1A1. However, ALDH1A1 was a better marker to define a subpopulation of tumor cells. Finally, neither ALDH1A1 nor CD44, alone or combined, were sufficient to determine the CSC population in HNSCC.

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“…Recently, Oct1 has been found to function as a sensor of both metabolic and stress/survival signals (131-134). In pancreatic islet cells, Oct1 senses intracellular cAMP levels (132).…”

Section: Functional Roles Of Oct In Specific Physiological Processesmentioning

confidence: 99%

“…Elevation of cAMP levels enhances Oct1 phosphorylation and shuttles Oct1 from the nucleus to the cytoplasm. Reduced nuclear Oct1 leads to increased expression of Cdx-2, which, in turn, regulates proglucagon and proinsulin expression (131, 132). Consistently, Oct1-deficient cells result in a coordinated metabolic shift with reduced glucose metabolism coupled with increased mitochondrial activity and amino acid oxidation (133).…”

Section: Functional Roles Of Oct In Specific Physiological Processesmentioning

confidence: 99%

Octamer-binding transcription factors: genomics and functions

Zhao¹

2013

Front Biosci

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The Octamer-binding proteins (Oct) are a group of highly conserved transcription factors that specifically bind to the octamer motif (ATGCAAAT) and closely related sequences that are found in promoters and enhancers of a wide variety of both ubiquitously expressed and cell type-specific genes. Oct factors belong to the larger family of POU domain factors that are characterized by the presence of a highly conserved bipartite DNA binding domain, consisting of an amino-terminal specific subdomain (POUS) and a carboxyl-terminal homeo-subdomain (POUH). Eleven Oct proteins have been named (Oct1-11), and currently, eight genes encoding Oct proteins (Oct1, Oct2, Oct3/4, Oct6, Oct7, Oct8, Oct9, and Oct11) have been cloned and characterized. Oct1 and Oct2 are widely expressed in adult tissues, while other Oct proteins are much more restricted in their expression patterns. Oct proteins are implicated in crucial and versatile biological events, such as embryogenesis, neurogenesis, immunity, and body glucose and amino acid metabolism. The aberrant expression and null function of Oct proteins have also been linked to various diseases, including deafness, diabetes and cancer. In this review, I will report both the genomic structure and major functions of individual Oct proteins in physiological and pathological processes.

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Oct-1 functions as a sensor for metabolic and stress signals

Cited by 16 publications

References 16 publications

Transcriptional Regulation of the HMGA1 Gene by Octamer-Binding Proteins Oct-1 and Oct-2

Transcriptional Regulation of the HMGA1 Gene by Octamer-Binding Proteins Oct-1 and Oct-2

Expression of ALDH1A1 and CD44 in primary head and neck squamous cell carcinoma and their value for carcinogenesis, tumor progression and cancer stem cell identification

Octamer-binding transcription factors: genomics and functions

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