Multiple mechanisms repress N-Bak mRNA translation in the healthy and apoptotic neurons

Jakobson, Madis; Llano, Olaya; Palgi, Jaan; Arumäe, Urmas

doi:10.1038/cddis.2013.297

Cited by 16 publications

(15 citation statements)

References 54 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Whether or not N-BAK functions as a BH3-only protein is still in question. Forced expression of N-BAK in tissue culture cells promotes apoptosis (Sun et al, 2003; Uo et al, 2005), but endogenously, N - Bak transcripts are in low abundance, and may be translationally repressed through various mechanisms (Jakobson et al, 2012, 2013). Preliminary studies done by our group indicates that N - Bak / N - BAK transcripts are present in retinal neurons of mice and non-human primates.…”

Section: The Bcl2 Gene Familymentioning

confidence: 99%

BAX to basics: How the BCL2 gene family controls the death of retinal ganglion cells

Maes

Schlamp

Nickells

2017

Progress in Retinal and Eye Research

155

120

View full text Add to dashboard Cite

Retinal ganglion cell (RGC) death is the principal consequence of injury to the optic nerve. For several decades, we have understood that the RGC death process was executed by apoptosis, suggesting that there may be ways to therapeutically intervene in this cell death program and provide a more direct treatment to the cells and tissues affected in diseases like glaucoma. A major part of this endeavor has been to elucidate the molecular biological pathways active in RGCs from the point of axonal injury to the point of irreversible cell death. A major component of this process is the complex interaction of members of the BCL2 gene family. Three distinct family members of proteins orchestrate the most critical junction in the apoptotic program of RGCs, culminating in the activation of pro-apoptotic BAX. Once active, BAX causes irreparable damage to mitochondria, while precipitating downstream events that finish off a dying ganglion cell. This review is divided into two major parts. First, we summarize the extent of knowledge of how BCL2 gene family proteins interact to facilitate the activation and function of BAX. This area of investigation has rapidly changed over the last few years and has yielded a dramatically different mechanistic understanding of how the intrinsic apoptotic program is run in mammalian cells. Second, we provided a comprehensive analysis of nearly two decades of investigation of the role of BAX in the process of RGC death, much of which has provided many important insights into the overall pathophysiology of diseases like glaucoma.

show abstract

Section: The Bcl2 Gene Familymentioning

confidence: 99%

BAX to basics: How the BCL2 gene family controls the death of retinal ganglion cells

Maes

Schlamp

Nickells

2017

Progress in Retinal and Eye Research

155

120

View full text Add to dashboard Cite

show abstract

“…Inclusion of this exon shifts Bak1 ORF and leads to the appearance of a PTC. Notably, the PTC containing mRNA does not appear to be targeted by NMD but its translation is repressed in part due to the presence of a downstream EJC [110] , [111] . Similarly, expression of the actin-related transcriptional repressor of muscle-specific genes Arp5 is controlled by a choice between two alternative 3′ splice sites (ss) in exon 7 [109] .…”

Section: The Orf Regionmentioning

confidence: 99%

Non-coding functions of alternative pre-mRNA splicing in development

Mockenhaupt

Makeyev

2015

Seminars in Cell & Developmental Biology

View full text Add to dashboard Cite

A majority of messenger RNA precursors (pre-mRNAs) in the higher eukaryotes undergo alternative splicing to generate more than one mature product. By targeting the open reading frame region this process increases diversity of protein isoforms beyond the nominal coding capacity of the genome. However, alternative splicing also frequently controls output levels and spatiotemporal features of cellular and organismal gene expression programs. Here we discuss how these non-coding functions of alternative splicing contribute to development through regulation of mRNA stability, translational efficiency and cellular localization.

show abstract

“…However, the N-Bak protein is not expressed in sympathetic neurons and this is due to translational repression mediated by sequences in the 5′- and 3′-UTRs of the N-Bak mRNA. 44 , 45 …”

Section: Ngf Withdrawal Activates the Mitochondrial (Intrinsic) Pathwmentioning

confidence: 99%

Programmed cell death during neuronal development: the sympathetic neuron model

Kristiansen

Ham

2014

Cell Death Differ

View full text Add to dashboard Cite

Developing sympathetic neurons of the superior cervical ganglion are one of the best studied models of neuronal apoptosis. These cells require nerve growth factor (NGF) for survival at the time that they innervate their final target tissues during late embryonic and early postnatal development. In the absence of NGF, developing sympathetic neurons die by apoptosis in a transcription-dependent manner. Molecular studies of sympathetic neuron apoptosis began in the 1980s. We now know that NGF withdrawal activates the mitochondrial (intrinsic) pathway of apoptosis in sympathetic neurons cultured in vitro, and the roles of caspases, Bcl-2 (B-cell CLL/lymphoma 2) family proteins and XIAP (X-linked inhibitor of apoptosis protein) have been extensively studied. Importantly, a considerable amount has also been learned about the intracellular signalling pathways and transcription factors that regulate programmed cell death in sympathetic neurons. In this article, we review the key papers published in the past few years, covering all aspects of apoptosis regulation in sympathetic neurons and focusing, in particular, on how signalling pathways and transcription factors regulate the cell death programme. We make some comparisons with other models of neuronal apoptosis and describe possible future directions for the field.

show abstract

Multiple mechanisms repress N-Bak mRNA translation in the healthy and apoptotic neurons

Cited by 16 publications

References 54 publications

BAX to basics: How the BCL2 gene family controls the death of retinal ganglion cells

BAX to basics: How the BCL2 gene family controls the death of retinal ganglion cells

Non-coding functions of alternative pre-mRNA splicing in development

Programmed cell death during neuronal development: the sympathetic neuron model

Contact Info

Product

Resources

About