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TRIM71 acts through post-transcriptional repression of Lin28B and subsequent modulation of let-7-HMGA2 signaling during tumorigenesis to potentially function as a tumor suppressor.
Studies indicate most-studied TRIpartite Motif (TRIM)-NHL proteins TRIM2, TRIM3, TRIM32 and TRIM71, and their mutations have been linked to diseases.
Consistent with the let-7 microRNA stimulatory role of TRIM71 via Lin28B polyubiquitination.
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The stem cell E3-ligase Lin-41 promotes liver cancer progression through inhibition of microRNA-mediated gene silencing.
Trim71 cooperates with microRNAs to repress Cdkn1a expression and promote embryonic stem cell proliferation
Repression of human TRIM71 and the zebrafish lin-41 ortholog was abolished when predicted let-7 target sites were mutated. Regulation of TRIM71 expression by let-7 seems to have been evolutionarily conserved.
A TRIM71 binding long noncoding RNA Trincr1 represses FGF/ERK signaling in embryonic stem cells.
LIN41 interacts with p53, controls its abundance by ubiquitination and antagonizes p53-dependent pro-apoptotic and pro-differentiation responses. In vivo, lack of LIN41 is associated with upregulation of Grhl3 and widespread caspase-3 activation, 2 downstream effectors of p53 with essential roles in neural tube closure.
suggest that Trim71 keeps priming steps of differentiation in check, which do not pre-require a loss of the pluripotency network in ES cells
Two well-known E3 ubiquitin ligases, Trim25 (also called Efp) and Trim71 (also called Lin41), are validated as RNA-binding proteins, revealing a potential link between RNA biology and protein-modification pathways.
mLin41 acts as a temporal regulator to promote neural progenitor cell maintenance, not via the regulation of AGO2 stability, but through FGF signaling.
The transcripts of mlin-41 and the protein level in mouse adult tissues and embryos from 9.5 to 13 days were detected by RT-PCR and western blot.
Lin-41 is genetically and biochemically downstream of both the Shh and Fgf signaling pathways and is expressed in three phases over developmental time and most notably is associated with the developing autopod.
lin-41 is temporally regulated by miRNAs in order to direct key developmental events such as limb formation.
Strong loss of function Mlin41 gene-trap mutants demonstrated a striking neural tube closure defect during development, and embryonic lethality.
demonstrate the presence of mLin41 protein in several stem cell niches, including the embryonic ectoderm, epidermis and male germ line.
May be involved in controlling the timing of organ formation during development (By similarity).
E3 ubiquitin-protein ligase TRIM71
, abnormal cell LINeage LIN-41
, homolog of C. elegans Lin-41
, protein lin-41 homolog
, tripartite motif-containing 71
, tripartite motif-containing protein 71
, B-box zinc finger, Filamin and NHL repeat containing protein (123.8 kD) (lin-41)
, Drosophila dappled/ vertebrate TRipartite Motif protein related
, lin-41 homolog