Mouse Atf5: Molecular Cloning of Two Novel mRNAs, Genomic Organization, and Odorant Sensory Neuron Localization

Hansen, Malene Bredahl; Mitchelmore, Cathy; Kjærulff, Karen M.; Rasmussen, Thomas; Pedersen, Karen M.; Jensen, Niels Rosendal

doi:10.1006/geno.2002.6838

Cited by 59 publications

(75 citation statements)

References 26 publications

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“…To generalize these results, future studies should be conducted to confirm the relationship between ATF5 expression and invasiveness in other cancer cell types. Previous studies suggested that ATF5 mRNA expression is observed in many different mouse [16] and human [17] tissues. We also showed that ATF5 increased the invasive activity of various cancer cell lines such as fibrosarcoma, lung, breast, cervical, gastric, and pancreatic cells.…”

Section: Discussionmentioning

confidence: 98%

Role of ATF5 in the invasive potential of diverse human cancer cell lines

Nukuda

Endoh

Yasuda

et al. 2016

Biochemical and Biophysical Research Communications

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Activating transcription factor 5 (ATF5) is a member of the ATF/cAMP response element-binding protein family. Our research group recently revealed that ATF5 expression increases the invasiveness of human lung carcinoma cells. However, the effects of ATF5 on the invasive potential of other cancer cells lines remain unclear.Therefore, in this study, we investigated the role of ATF5 in the invasive activity of diverse human cancer cell lines. Invasiveness was assessed using Matrigel invasion assays. ATF5 knockdown resulted in decreased invasiveness in seven of eight cancer cell lines tested. These results suggest that ATF5 promotes invasiveness in several cancer cell lines. Furthermore, the roles of ATF5 in the invasiveness were evaluated in three-dimensional (3D) culture conditions. In 3D collagen gel, HT-1080 and MDA-MB-231 cells exhibited high invasiveness, with spindle morphology and high invasion speed. In both cell lines, knockdown of ATF5 resulted in rounded morphology and decreased invasion speed. Next, we showed that ATF5 induced integrin-2 and integrin-1 expression and that the depletion of integrin-2 or integrin-1 resulted in round morphology and decreased invasion speed. Our results suggest that ATF5 promotes invasion by inducing the expression of integrin-2 and integrin-1 in several 3 human cancer cell lines. ATF5 regulates cell morphology in a 3D collagen gel via integrin-21 activity. Keywords

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Section: Discussionmentioning

confidence: 98%

Role of ATF5 in the invasive potential of diverse human cancer cell lines

Nukuda

Endoh

Yasuda

et al. 2016

Biochemical and Biophysical Research Communications

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“…Expression of the ISR transcriptional regulator ATF5 features two different mRNA isoforms (79). The more abundant transcript, ATF5␣, contains two uORFs that serve to promote preferential translation by delayed translation reinitiation (36,80).…”

Section: Other Complexities Of Gene Expression Regulated By Uorfsmentioning

confidence: 99%

“…ATF5␤ encodes the same ATF5 CDS, but contains an alternative 5Ј-leader that does not contain any conserved uORFs and is not translationally regulated in a stress-dependent manner (80). Thus, expression of ATF5 can also be modulated through the differential production of mRNA isoforms (79). Recent genome-wide evidence has suggested that regulation of translation through mRNA splicing also plays a significant role in the presence of different 5Ј-leaders in mRNAs that can affect translational expression (78).…”

Section: Other Complexities Of Gene Expression Regulated By Uorfsmentioning

confidence: 99%

Upstream Open Reading Frames Differentially Regulate Gene-specific Translation in the Integrated Stress Response

Young

Wek

2016

Journal of Biological Chemistry

337

313

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Translation regulation largely occurs during initiation, which features ribosome assembly onto mRNAs and selection of the translation start site. Short, upstream ORFs (uORFs) located in the 5-leader of the mRNA can be selected for translation. Multiple transcripts associated with stress amelioration are preferentially translated through uORF-mediated mechanisms during activation of the integrated stress response (ISR) in which phosphorylation of the ␣ subunit of eIF2 results in a coincident global reduction in translation initiation. This review presents key features of uORFs that serve to optimize translational control that is essential for regulation of cell fate in response to environmental stresses.Multiple genome-wide analyses, including those utilizing ribosome and polysome profiling and mass spectrometry approaches, have provided evidence demonstrating that translation is a major regulator of gene expression (1-5). In addition to protein coding sequences (CDSs), 2 another class of ORFs suggested to be translated at high frequency consists of short, upstream ORFs (uORFs) that are located within the 5Ј-leader of mRNAs (3-6). Over 40% of mammalian mRNAs contain uORFs, illustrating that uORFs are prevalent genome-wide and can serve as major regulators of translation (5,7,8). Approximation of uORF prevalence has relied upon the use of an AUG to denote the uORF start codon; however, recent ribosome profiling studies indicate that non-canonical initiation codons (e.g. CUG, UUG, and GUG) can also serve as competent sites of translation initiation (3, 4, 6). These findings suggest that the magnitude of uORF prevalence and the contribution of uORF translation in the regulation of gene expression have likely been underestimated.Typically, uORFs are considered to be inhibitors of downstream translation initiation at CDSs. The inhibitory effect of uORFs is attributed to the fact that in eukaryotes the 43S preinitiation complex binds to the 5Ј-cap structure of the mRNA, then scans processively 5Ј to 3Ј and initiates translation at the first encountered initiation codon that is in an optimal context (9). The 43S preinitiation complex is composed of multiple factors including eIF3, eIF1, eIF1A, the eIF2⅐GTP⅐Met-tRNA i Met ternary complex, and the small 40S ribosomal subunit (10). Disassociation of the eIF2 ternary complex and other critical initiation factors during translation of constitutively repressing uORFs is suggested to be the cause of the low levels of subsequent translation reinitiation at downstream coding sequences.Although uORFs can serve as repressors of CDS translation in a constitutive manner, there are also examples of uORFs that serve as dampeners in a controlled fashion or even promote translation initiation at the CDS in response to environmental stresses (4, 5, 11). Based on these studies, uORFs can have the following core properties that are critical for translational control (Fig. 1). 1) They enhance reinitiation after uORF translation, allowing for degrees of translation initiation at the downstre...

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“…ATF5 ATF4 activates transcription of ATF5 (Zhou et al 2008), which was first cloned as a factor in developing sensory neurons of the olfactory epithelium (Hansen et al 2002). ATF5 inhibits differentiation of neuroprogenitor cells into neurons (Angelastro et al 2003) and astrocytes ) and of oligodendrocyte precursors into oligodendrocytes .…”

Section: Additional Tfsmentioning

confidence: 99%

Physiological/pathological ramifications of transcription factors in the unfolded protein response

2017

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Numerous environmental, physiological, and pathological insults disrupt protein-folding homeostasis in the endoplasmic reticulum (ER), referred to as ER stress. Eukaryotic cells evolved a set of intracellular signaling pathways, collectively termed the unfolded protein response (UPR), to maintain a productive ER protein-folding environment through reprogramming gene transcription and mRNA translation. The UPR is largely dependent on transcription factors (TFs) that modulate expression of genes involved in many physiological and pathological conditions, including development, metabolism, inflammation, neurodegenerative diseases, and cancer. Here we summarize the current knowledge about these mechanisms, their impact on physiological/pathological processes, and potential therapeutic applications.

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Mouse Atf5: Molecular Cloning of Two Novel mRNAs, Genomic Organization, and Odorant Sensory Neuron Localization

Cited by 59 publications

References 26 publications

Role of ATF5 in the invasive potential of diverse human cancer cell lines

Role of ATF5 in the invasive potential of diverse human cancer cell lines

Upstream Open Reading Frames Differentially Regulate Gene-specific Translation in the Integrated Stress Response

Physiological/pathological ramifications of transcription factors in the unfolded protein response

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