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Transcription factor that plays a key role in neuronal differentiation: acts as a pioneer transcription factor, accessing closed chromatin to allow other factors to bind and activate neural pathways. Directly binds the E box motif (5'-CANNTG-3') on promoters and promotes transcription of neuronal genes. The combination of three transcription factors, ASCL1, POU3F2/BRN2 and MYT1L, is sufficient to reprogram fibroblasts and other somatic cells into induced neuronal (iN) cells in vitro. Plays a role at early stages of development of specific neural lineages in most regions of the CNS, and of several lineages in the PNS. Essential for the generation of olfactory and autonomic neurons. Acts synergistically with FOXN4 to specify the identity of V2b neurons rather than V2a from bipotential p2 progenitors during spinal cord neurogenesis, probably through DLL4-NOTCH signaling activation. Involved in the regulation of neuroendocrine cell development in the glandular stomach.
基因功能參考文獻:
We address this paradox using basic helix-loop-helix (bHLH) transcription factors ASCL1, ASCL2, and MYOD1, crucial mediators of lineage specification..Although the ASCL factors and MYOD1 have some distinct DNA motif preference, it is not sufficient to explain the extent of the differential binding. All three factors can bind inaccessible chromatin and induce changes in chromatin accessibility and H3K27ac PMID: 29500235
a large subset of patient-derived glioblastoma stem cells (GSCs) express high levels of Achaete-scute homolog 1 (ASCL1), a proneural transcription factor involved in normal neurogenesis. PMID: 28712938
System analysis identified distinct and common functional networks governed by transcription factor ASCL1, in glioma and small cell lung cancer. PMID: 28742165
Results indicate transcription factor Ascl1 protein functionalized with intracellular protein delivery technology (Ascl1-IPTD) as a powerful tool for engineering neural tissue from pluripotent stem cells. PMID: 27138845
knocking down achaete-scute complex homologue-1 expression could significantly suppress the proliferation, migration, and invasion of laryngeal carcinoma cell in vitro and disorder epithelial-mesenchymal transformation-associated protein expression. PMID: 28618959
we found that CpG_6.7.8 of the achaete-scute homolog 1 CpG island is frequently hypermethylated in early-stage pulmonary neuroendocrine tumors, and this aberrant hypermethylation is negatively correlated with achaete-scute homolog 1 expression in this tumor spectrum PMID: 28621224
the first comprehensive high-resolution information on the structural propensities and conformational dynamics of Ascl1, is reported. PMID: 28402879
ASCL1 expression may determine the cell behaviors of SCLC partly through modifying EMT phenotypes. PMID: 27785690
This report identifies novel roles for the transcription factor Ascl1 in enteric gliogenesis and neurogenesis PMID: 27076429
ASCL1 expression is regulated by BRD4 is frequently overexpressed in small cell lung cancer. PMID: 26253517
Data show that chrysin suppressed cell proliferation and reducing expression of achaete-scute complex-like 1 (ASCL1) and the neuroendocrine biomarker chromogranin A (CgA). PMID: 26403073
hASH1 is a specific marker to distinguish neuroendocrine tumors from squamous cell carcinomas and adenocarcinomas PMID: 26596584
marker for neurogenic potential in cultured retinal progenitor cells PMID: 26292211
Achaete-scute homolog 1 (ASCL1), a transcription factor required for proper development of pulmonary neuroendocrine cells, is essential for the survival of a majority of lung cancers with neuroendocrine features. PMID: 25267614
data suggest that a prominent down-regulation of hnRNP-A2/B1 during hypoxia is associated with the post-transcriptional suppression of hASH1 synthesis. PMID: 25124043
ASCL1 and RET expression defines a clinically relevant subgroup of lung adenocarcinoma characterized by neuroendocrine differentiation. PMID: 24037524
lentiviral overexpression of transcription factors ASCL1, SOX10, and NKX2.2 in NPCs was sufficient to induce Sox10 enhancer activity, OPC mRNA, and protein expression consistent with OPC fate PMID: 24982138
ASCL1 Promotes Wnt Signaling Directly by Repressing DKK1. PMID: 23707066
BRN2 is a higher level regulator than ASCL1 and ND1 and BRN2 might be involved in aggressiveness of small cell lung cancer. PMID: 23530560
Gene expression profiling revealed that permissive lines are typified by lower expression of the early neurogenic transcription factor ASCL1 and, conversely, by higher expression of the late neurogenic transcription factor NEUROD1. PMID: 23739064
ASH1 overexpression in prostate cancer cells promotes neuroendocrine differentiation and increased cell viability. PMID: 23657976
Achaete-scute homolog 1 may be proposed as a diagnostic marker of poor differentiation and may help to differentiate neuroendocrine carcinomas from neuroendocrine tumors in difficult cases. PMID: 23375646
Ascl1 modulates multiple steps of oligodendrocyte precursor cell development in the postnatal brain and in response to demyelinating insults. PMID: 23739972
Ascl1 directly regulates expression of matrix metalloproteinase-7 and O(6)-methylguanine-DNA methyltransferase. PMID: 23300791
The ASCL1 knock-down gene set also classified the 171 adenocarcinomas into three subtypes and this NE subtype also had the poorest prognosis. PMID: 21737174
Among human primary tumors, 2/2 SCLC, 5/5 pulmonary carcinoids, and 10/41 non-SCLC (only 4 of which had NE features) were positive for hASH1 by immunohistochemistry and RNA-RNA in situ hybridization. PMID: 21684625
hASH-1 expression occurs in breast cancers with neuroendocrine differentiation regardless of the extent of the NE cell population, and it is restricted to a subset of tumor cells having a low proliferative potential. PMID: 22422124
Dual-luciferase assays showed that ASCL1 activated the expression of miR-375 by binding to the three E-box elements in the miR-375 promoter. These results imply a role of ASCL1 in SCLC via the upregulation of miR-375. PMID: 22172490
miR-375 is a key downstream effector of ASH1 function in lung cancer cells PMID: 21856745
The present results suggest that a transcriptional complex of LMO3 and HEN2 may contribute to the genesis and malignant phenotype of neuroblastoma by inhibiting HES1 which suppresses the transactivation of Mash1. PMID: 21573214
HASH1 down-regulation is associated with cell proliferation, thereby resulting in uterine carcinogenesis. PMID: 21495212
ASCL1-pathway is responsible for the up-regulation of IGF2 during neuroblastoma differentiation. PMID: 20842449
deletional rearrangement of the TCR delta gene disrupted the hypothetical gene C12orf42 and brought the Achaete-scute complex homolog 1 gene into proximity of the TRA enhancer, which is overexpressed in thyroid and lung cancers PMID: 20659153
hASH1 is a new kind of highly specific markers of pulmonary neuroendocrine tumours, and may be applied to clinical pathology diagnosis of the pulmonary neuroendocrine tumors. PMID: 20677557
report the analysis of 9 highly conserved putative enhancers in a 64kb interval encompassing the human ASCL1 locus PMID: 20206680
Supratentorial PNETs expressed significantly higher levels of SOX2, NOTCH1, ID1, and ASCL-1 transcripts. PMID: 20515335
Our data indicate a specific role for ASCL1 in regulating the expression of the CHRNA5/A3/B4 lung cancer susceptibility locus. This regulation may contribute to the predicted role that ASCL1 plays in SCLC tumorigenesis. PMID: 20124469
these support the role of the polyglutamine length variants in the MASH1 gene in Parkinson's disease susceptibility. PMID: 20097173
HASH1 mRNA expression levels in SCLC clinical samples were 1,000-fold higher than in the NSCLC samples, and this method could contribute to diagnosis based on molecular profiling of tumors. PMID: 11948117
We also studied the proneural HASH-1 gene and identified a heterozygous nucleotide substitution in three CCHS patients PMID: 14532329
HASH1 appears to be important in the endocrine phenotype of medullary thyroid carcinoma (MTC) tumors and may serve as a molecular target for the treatment of patients with MTC. PMID: 14668716
ASH1 is a neuroendocrine marker whose expression is largely conserved in normal and neoplastic pituitary cells. PMID: 14759067
the hASH1 mRNA level might represent a useful tool for distinguishing esthesioneuroblastoma from poorly differentiated tumors of the sinonasal region PMID: 15272537
Up-Regulation of ASCL1 is associated with gastrointestinal neuroendocrine carcinomas PMID: 15701827
The present genetic data may thus suggest that polyglutamine length polymorphisms in ASCL1 could influence predispositions to PD through the fine-tuning of LC integrity. PMID: 16021468
RaF-1 activation causes cessation of hASH-1 expression PMID: 16029117
Upregulation of ASCL1 and inhibition of Notch signaling pathway characterize progressive astrocytoma PMID: 16103883
Knockdown of ASH1 gene in lung neoplasm cells in vitro suppressed growth by increasing apoptosis. PMID: 17507989
In prostate cancers with neuroendocrine differentiation...hASH1 transcript levels in androgen deprivation-treated compared with untreated patients PMID: 18311112
ASH1 functions as a dual transcription factor by activating neuroendocrine differentiation markers and also repressing putative tumor suppressors. PMID: 18339843