Analysis of the guinea-pig estrogen-regulated gec1/GABARAPL1 gene promoter and identification of a functional ERE in the first exon

Vernier-Magnin, Sandrine; Némos, Christophe; Mansuy, Virginie; Tolle, Fabrice; Guichard, Laure; Delage-Mourroux, Régis; Jouvenot, Michèle; Fraîchard, Annick

doi:10.1016/j.bbaexp.2005.05.002

Cited by 8 publications

(6 citation statements)

References 41 publications

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“…Also for GABARAPL1, 6 transcription factors have been identified. GABARAPL1 is induced in response to the transcription factors ATF4 (100), GATA1 (107), C/EBPb (118), FOXO1 (108, 111), FOXO3 (107, 110, 111), and estrogen receptor activation (123). Furthermore, GABARAP expression is controlled by GATA1 (107), CHOP (113), p38α (124), and p73 (125) transcriptional activity.…”

Section: Functions Of Lc3/gabarap Family Proteins In Autophagymentioning

confidence: 99%

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LC3/GABARAP family proteins: autophagy‐(un)related functions

et al. 2016

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From yeast to mammals, autophagy is an important mechanism for sustaining cellular homeostasis through facilitating the degradation and recycling of aged and cytotoxic components. During autophagy, cargo is captured in double-membraned vesicles, the autophagosomes, and degraded through lysosomal fusion. In yeast, autophagy initiation, cargo recognition, cargo engulfment, and vesicle closure is Atg8 dependent. In higher eukaryotes, Atg8 has evolved into the LC3/GABARAP protein family, consisting of 7 family proteins [LC3A (2 splice variants), LC3B, LC3C, GABARAP, GABARAPL1, and GABARAPL2]. LC3B, the most studied family protein, is associated with autophagosome development and maturation and is used to monitor autophagic activity. Given the high homology, the other LC3/GABARAP family proteins are often presumed to fulfill similar functions. Nevertheless, substantial evidence shows that the LC3/GABARAP family proteins are unique in function and important in autophagy-independent mechanisms. In this review, we discuss the current knowledge and functions of the LC3/GABARAP family proteins. We focus on processing of the individual family proteins and their role in autophagy initiation, cargo recognition, vesicle closure, and trafficking, a complex and tightly regulated process that requires selective presentation and recruitment of these family proteins. In addition, functions unrelated to autophagy of the LC3/GABARAP protein family members are discussed.-Schaaf, M. B. E., Keulers, T. G, Vooijs, M. A., Rouschop, K. M. A. LC3/GABARAP family proteins: autophagy-(un)related functions.

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Section: Functions Of Lc3/gabarap Family Proteins In Autophagymentioning

confidence: 99%

“…LC3B is the most studied and therefore best understood member of the LC3/GABARAP family. So far, (107,110,111), and estrogen receptor activation (123). Furthermore, GABARAP expression is controlled by GATA1 (107), CHOP (113), p38a (124), and p73 (125) transcriptional activity.…”

Section: Other Regulatory Mechanismsmentioning

confidence: 99%

LC3/GABARAP family proteins: autophagy‐(un)related functions

et al. 2016

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“…Unlike other GABARAP or MAP1LC3/LC3 family members, GABARAPL1 possesses an estrogen-responsive element and can be activated by estradiol-17b, via ESR1/estrogen receptor a. 29 Reduced GABAR-APL1 expression has been reported in various cancer cell lines compared to normal tissues, 30 and is correlated with higher histological grade in breast adenocarcinoma patients. 31 A mechanism has yet to be proposed for the association of reduced GABAR-APL1 with increased pathogenesis in breast cancer; however, reduced autophagy function seems unlikely given the redundancy of GABARAPL1 in autophagosome biogenesis.…”

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confidence: 99%

Cross-cancer profiling of molecular alterations within the human autophagy interaction network

et al. 2015

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Aberrant activation or disruption of autophagy promotes tumorigenesis in various preclinical models of cancer, but whether the autophagy pathway is a target for recurrent molecular alteration in human cancer patient samples is unknown. To address this outstanding question, we surveyed 211 human autophagy-associated genes for tumorrelated alterations to DNA sequence and RNA expression levels and examined their association with patient survival outcomes in multiple cancer types with sequence data from The Cancer Genome Atlas consortium. We found 3 (RB1CC1/FIP200, ULK4, WDR45/WIPI4) and one (ATG7) core autophagy genes to be under positive selection for somatic mutations in endometrial carcinoma and clear cell renal carcinoma, respectively, while 29 autophagy regulators and pathway interactors, including previously identified KEAP1, NFE2L2, and MTOR, were significantly mutated in 6 of the 11 cancer types examined. Gene expression analyses revealed that GABARAPL1 and MAP1LC3C/LC3C transcripts were less abundant in breast cancer and non-small cell lung cancers than in matched normal tissue controls; ATG4D transcripts were increased in lung squamous cell carcinoma, as were ATG16L2 transcripts in kidney cancer. Unsupervised clustering of autophagy-associated mRNA levels in tumors stratified patient overall survival in 3 of 9 cancer types (acute myeloid leukemia, clear cell renal carcinoma, and head and neck cancer). These analyses provide the first comprehensive resource of recurrently altered autophagy-associated genes in human tumors, and highlight cancer types and subtypes where perturbed autophagy may be relevant to patient overall survival.

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“…Basal promoter activity assay showed that the maximal promoter activity could be achieved with a Ϫ1262/ϩ7 construct and that bigger constructs yielded less promoter activity. This effect is observed in many mammalian genes (41,43), and it has been attributed to the presence of inhibitory domains of the active promoters in upstream sequences (43,44). A similar pattern of basal activity displayed by the various size constructs in different cell lines suggests that basal promoter activity is driven by a similar pol II complex regardless of the cell line.…”

Section: Discussionmentioning

confidence: 65%

Regulation of Mouse Slo Gene Expression

Kundu

Alioua

Stefani

et al. 2007

Journal of Biological Chemistry

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The large conductance, voltage-and Ca 2؉-activated K ؉ channel plays key roles in diverse body functions influenced by estrogen, including smooth muscle and neural activities. In mouse (m), estrogen up-regulates the transcript levels of its pore-forming ␣-subunit (Slo, KCNMA1), yet the underlying genomic mechanism(s) is(are) unknown. We first mapped the promoters and regulatory motifs within the mSlo 5-flanking sequence to subsequently identify genomic regions and mechanisms required for estrogen regulation. mSlo gene has at least two TATA-less promoters with distinct potencies that may direct mSlo transcription from multiple transcription start sites. These qualities mark mSlo as a prototype gene with promoter plasticity capable of generating multiple mRNAs and the potential to adapt to organismal needs. mSlo promoters contain multiple estrogen-responsive sequences, e.g. two quasiperfect estrogen-responsive elements, ERE1 and ERE2, and Sp1 sites. Accordingly, mSlo promoter activity was highly enhanced by estrogen and blocked by estrogen antagonist ICI 182,780. When promoters are embedded in a 4.91-kb backbone, estrogen responsiveness involves a classical genomic mechanism, via ERE1 and ERE2, that may be complemented by Sp factors, particularly Sp1. Simultaneous but not individual ERE1 and ERE2 mutations caused significant loss of estrogen action. ERE2, which is closer to the proximal promoter, up-regulates this promoter via a classical genomic mechanism. ERE2 strategic position together with ERE1 and ERE2 independence and Sp contribution should ensure mSlo estrogen responsiveness. Thus, the mSlo gene seems to have uniquely evolved to warrant estrogen regulation. Estrogen-mediated mSlo genomic regulation has important implications on long term estrogenic effects affecting smooth muscle and neural functions. . As a consequence, MaxiK channels are key regulators of vital body functions such as, blood flow, neural function, and uresis (1-3). MaxiK channels are formed by four pore-forming ␣-subunits (Slo) that can associate with regulatory ␤-subunits (4). The ␣-subunit is expressed from a single copy gene in all studied species known as KCNMA1 or Slo. In mouse, it is present in chromosome 14 and has 27 constitutive exons, which are evolutionarily conserved.Knock-out mouse models have highlighted the importance of Slo expression in blood pressure regulation (5), hearing (6), urinary bladder contraction (7), erectile function (8), and neurological disorders (9). Furthermore, a mutation in the human gene has been linked to coexistent generalized epilepsy and paroxysmal dyskinesia (10).Defining the mechanisms that rule Slo gene expression is key to understanding the basis of Slo channel function. Several publications in recent years show that Slo transcript levels can be under the control of sex hormones and pregnancy. For example, mSlo transcript levels were up-regulated with the advancement of pregnancy in mouse myometrium (11, 12) likely due to the change in sex hormone levels. Consistent with this idea, mSlo transcr...

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Analysis of the guinea-pig estrogen-regulated gec1/GABARAPL1 gene promoter and identification of a functional ERE in the first exon

Cited by 8 publications

References 41 publications

LC3/GABARAP family proteins: autophagy‐(un)related functions

LC3/GABARAP family proteins: autophagy‐(un)related functions

Cross-cancer profiling of molecular alterations within the human autophagy interaction network

Regulation of Mouse Slo Gene Expression

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