Sequence of a 131-kb Region of 5q13.1 Containing the Spinal Muscular Atrophy Candidate Genes SMN and NAIP

Chen, Qianfa; Baird, Stephen; Mahadevan, Mani S.; Besner-Johnston, Anne; Farahani, Reza Masteri; Xuan, J.Y.; Kang, Xin; Lefebvre, Charles; Ikeda, Joh‐E; Korneluk, Robert G.; MacKenzie, Alex

doi:10.1006/geno.1997.5141

Cited by 56 publications

(44 citation statements)

References 32 publications

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“…This gene was found by virtue of it's absence from the majority of infants with the most severe form of the pediatric neurodegenerative disorder known as spinal muscular atrophy (SMA, Roy et al, 1995). This autosomal recessive condition is caused by Roy et al, 1995;Chen et al, 1998;mNAIP1-6, mouse NAIP-1 through 6 (AF007769) Yaraghi et al, 1998; NAIP-rs 1 through 6, NAIP related sequence 1 (U66324), 2 (U66325), 3 (U66326), 4 (U66327), 5 (U66328), 6 (U66329) Scharf et al, 1996; rNAIP, Rat NAIP (partial cDNA) Korneluk et al, (unpublished); HIAP1, human IAP1 (U45878) Liston et al, 1996; cIAP2, cellular IAP2 (L49432) Rothe et al, 1995; MIHC, mammalian IAP homolog C (U37546) Uren et al, 1996; hITA, human inhibitor of T-cell apoptosis, Nicholl et al, 1996; MIAP1, mouse IAP1 (U88908) Liston et al, 1997;RIAP1, rat IAP1 Holcik et al, (unpublished); PIAP, porcine IAP (U79142) Stehlik et al, 1998b; ITA, inhibitor of T-cell apoptosis (U27466) Digby et al, 1996;ch-IAP1, chicken a severe loss of motor neurons which results in fatal accid paralysis (Dubowitz, 1995). While the contiguous SMN gene has been found to be causative of SMA , the tissue expression of NAIP (Xu et al, 1997a) combined with its strong in vitro (Liston et al, 1996) and in vivo (Xu et al, 1997b) neuroprotective eect make it a likely candidate for modi®cation of the SMA phenotype.…”

Section: Non-viral Iapsmentioning

confidence: 99%

The inhibitors of apoptosis (IAPs) and their emerging role in cancer

LaCasse¹,

et al. 1998

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The inhibitor of apoptosis protein family has been characterized over the past 5 years, initially in baculovirus and more recently in metazoans. The IAPs are a widely expressed gene family of apoptotic inhibitors from both phylogenic and physiologic points of view. The diversity of triggers against which the IAPs suppress apoptosis is greater than that observed for any other family of apoptotic inhibitors including the bcl-2 family. The central mechanisms of IAP apoptotic suppression appear to be through direct caspase and pro-caspase inhibition (primarily caspase 3 and 7) and modulation of and by the transcription factor NF-kB. Although evidence for a direct oncogenic role for the IAPs has yet to be delineated, a number of lines of evidence point towards this class of protein playing a role in oncogenesis. The strongest evidence for IAP involvement in cancer is seen in the IAP called survivin. Although not observed in adult dierentiated tissue, survivin is present in most transformed cell lines and cancers tested to date. Survivin has been shown to inhibit caspase directly and apoptosis in general, moreover survivin protein levels correlate inversely with 5 year survival rates in colorectal cancer. Recent data has also implicated survivin in cell cycle control. The second line of evidence for IAP involvement in cancer comes from their emerging role as mediators and regulators of the anti-apoptotic activity of v-Rel and NF-kB transcription factor families. The IAPs have been shown to be induced by NF-kB or v-Rel in multiple cell lines and conversely, HIAP1 and HIAP2 have been shown to activate NF-kB possibly forming a positive feed-back loop. Overall a picture consistent with an IAP role in tumour progression rather than tumour initiation is emerging making the IAPs an attractive therapeutic target.Keywords: inhibitor of apoptosis; IAP; programmed cell death; BIR; RING ®nger; CARD; NAIP; survivin; NF-kB; caspase Part A. The IAP familyThe ®rst Inhibitor of Apoptosis (IAP) proteins were identi®ed in 1993 and 1994 in the baculoviruses Cydia pomonella granulosis virus (CpGV) and Orgyia pseudotsugata nuclear polyhedrosis virus (OpMNPV) by the laboratory of Lois Miller (Crook et al., 1993;Birnbaum et al., 1994). The Miller lab utilized an assay in which infection by a mutant strain of a third baculovirus, Autographa californica nuclear polyhedrosis virus (AcMNPV) results in an unconstrained host lepidopteran SF-21 cell apoptosis. (The natural host cell apoptotic response to viral infection is usually eectively suppressed by the infecting baculovirus). Employing this assay, the CpGV and OpMNPV genomes were screened for loci which would suppress this cell death, resulting in the identi®cation of founding members of a new class of anti-apoptotic genes encoding Cp-IAP and Op-IAP, two proteins which share both homology and the ability to block apoptosis by a wide number of apoptotic triggers (Tables 1, 2 and 5). BIR and RING Zn ®nger domainsThere exists in the baculoviral IAPs two de®ning motifs. The ®rst of these is the B...

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Section: Non-viral Iapsmentioning

confidence: 99%

The inhibitors of apoptosis (IAPs) and their emerging role in cancer

LaCasse¹,

et al. 1998

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“…Homozygous deletions of the SMN1 gene and variable copies of the SMN2 duplication in this region have been associated with various forms of spinal muscular atrophy and susceptibility to the disease 14,15 . Analysis of carriers and controls suggests extreme locus variability, but the underlying structural variation has never been documented at the sequence level 16 . We identified a complex arrangement of 311 pairwise alignments representing the SMA region (Fig.…”

Section: Sma Duplication Regionmentioning

confidence: 99%

The DNA sequence and comparative analysis of human chromosome 5

Schmutz¹,

Martin²,

Terry³

et al. 2004

Nature

114

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“…A second group of repressed transcripts consisted of components or suspected components of the splicing machinery, such as hnRNP H (Honore et al, 1995), a U1 small nuclear ribonucleoprotein 70K-subunit homolog (Elisei et al, 1993), U1 small nuclear RNPspeci®c C protein (Sillekens et al, 1988), Survival of Motor Neurons protein (SMN, Chen et al, 1998), which has been implicated in spliceosomal snRNP biogenesis (Fischer et al, 1997) and arginine-rich nuclear protein (Chaudhary et al, 1991).…”

Section: Effects On Rna and Protein Synthesismentioning

confidence: 99%

Expression profiling of glucocorticoid-treated T-ALL cell lines: rapid repression of multiple genes involved in RNA-, protein- and nucleotide synthesis

et al. 2001

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To arrive at a better understanding of the e ects of the glucocorticoid component of chemotherap#y protocols on lymphocytic leukemia cells, we analysed early responses of T-lymphocytic leukemia cell lines Jurkat and CEM-C7, both of which undergo apoptosis in response to dexamethasone, via gene chips. Among genes identi®ed as repressed, a notable cluster seemed to be of importance for the processes of transcription, mRNA splicing and protein synthesis. Consequently, we assessed time-resolved uptake of uridine and methionine to monitor RNA and protein synthesis, along with parameters quantifying apoptosis. Repression of uptake to about 65% of that in untreated cells preceded the ®rst sign of apoptosis by several hours in both cell lines. In addition to this general repression of RNA and protein synthesis, several genes were found to be regulated that may contribute to synergistic action of glucocorticoids with other components of frequently used chemotherapy protocols such as antimetabolites, methotrexate and alkylating agents. Oncogene (2001) 20, 4324 ± 4336.

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Sequence of a 131-kb Region of 5q13.1 Containing the Spinal Muscular Atrophy Candidate Genes SMN and NAIP

Cited by 56 publications

References 32 publications

The inhibitors of apoptosis (IAPs) and their emerging role in cancer

The inhibitors of apoptosis (IAPs) and their emerging role in cancer

The DNA sequence and comparative analysis of human chromosome 5

Expression profiling of glucocorticoid-treated T-ALL cell lines: rapid repression of multiple genes involved in RNA-, protein- and nucleotide synthesis

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