EIF3S4 Blocking Peptide
- Known as:
- EIF3S4 Blocking Peptide
- Catalog number:
- 33r-8672
- Product Quantity:
- USD
- Category:
- -
- Supplier:
- Fitzgerald industries international
- Gene target:
- EIF3S4 Blocking Peptide
Related genes to: EIF3S4 Blocking Peptide
- Gene:
- EIF3G NIH gene
- Name:
- eukaryotic translation initiation factor 3 subunit G
- Previous symbol:
- EIF3S4
- Synonyms:
- eIF3-delta, eIF3-p44, eIF3g
- Chromosome:
- 19p13.2
- Locus Type:
- gene with protein product
- Date approved:
- 1998-11-26
- Date modifiied:
- 2015-12-04
Related products to: EIF3S4 Blocking Peptide
Related articles to: EIF3S4 Blocking Peptide
- Skeletal muscle adaptation to physiological and pathological stressors requires precise coordination of protein synthesis and mitochondrial function. While the roles of canonical translation regulators such as eIF2α and 4E-BP1 in exercise-induced protein synthesis modulation are well established, the contribution of eIF3, the largest eukaryotic initiation factor complex, to muscle stress responses remains poorly understood. Eukaryotic initiation factor 3 (eIF3) regulates mRNA translation and mitochondrial homeostasis, yet how individual eIF3 subunits respond to distinct modes of skeletal muscle stress remains unclear. Here, we systematically characterized eIF3 dynamics and mitochondrial function using two complementary mouse models: acute exhaustive training and dexamethasone (DEX)-induced atrophy. Integrated proteomic, transcriptional, and imaging analyses revealed a biphasic regulatory pattern: DEX treatment caused broad downregulation of eIF3a, eIF3b, eIF3c, eIF3g, and eIF3l, concurrent with comprehensive mitochondrial electron transport chain (ETC) impairment, while acute training selectively decreased eIF3d, eIF3e, eIF3g, and eIF3l but uniquely preserved eIF3f expression alongside adaptive ETC remodeling. This differential response pattern distinguishes eIF3 from other stress-responsive translation factors, as eIF2α phosphorylation typically causes global translation suppression whereas eIF3 dysregulation selectively impairs mitochondrial protein synthesis. Notably, eIF3f preservation under both conditions suggests a compensatory mechanism to maintain translational capacity. siRNA-mediated knockdown of eIF3e or eIF3f in C2C12 myotubes demonstrated their differential effects on mitochondrial protein expression and atrophy signaling, with eIF3f knockdown causing more severe mitochondrial protein suppression. Seahorse XF analysis confirmed that eIF3 subunit loss directly impairs mitochondrial oxygen consumption, while SUnSET assays demonstrated attenuated global protein synthesis upon eIF3e or eIF3f depletion. Furthermore, eIF3 knockdown suppressed mTORC1 signaling (p-mTOR, p-4EBP1, p-S6K, p-S6) and differentially modulated ubiquitin-proteasome activity without altering bulk autophagy. These findings establish eIF3 as a molecular integrator linking translational control to mitochondrial integrity in skeletal muscle physiology, positioning this complex as a potential therapeutic target for conditions ranging from exercise-induced adaptation to muscle wasting disorders. - Source: PubMed
Lin YingyingXia JianingLi ManZhang JunhaoMu YonghaoLing LenianLu MinghaoWang JiahuanLiao KexinCai Yefeng - Programmed cell death 4 (PDCD4) protein is a tumour suppressor protein that inhibits mRNA translation by inhibiting RNA helicase, eukaryotic initiation factor 4A (eIF4A). We have previously reported that PDCD4 interacts with the internal ribosome entry site (IRES) element of B-cell lymphoma extra-large (Bcl-xL) mRNA and inhibits its IRES-mediated translation initiation. S6 kinase (S6K)-mediated phosphorylation of PDCD4 activates its degradation and derepresses IRES-mediated translation initiation of Bcl-xL mRNA. eIF3F (one of the subunits of eIF3 complex) was reported to recruit S6K to phosphorylate eIF3G. Therefore, we investigated the possibility of co-regulation of PDCD4 and eIF3F by S6K and the regulation of IRES-mediated translation initiation by PDCD4-eIF3F. Here, we demonstrated that PDCD4 interacts with several subunits of eIF3. Specifically, eIF3F directly interacts with PDCD4 in an RNA-independent manner. Depletion of PDCD4 in glioblastoma (GBM) cells resulted in decreased levels of certain eIF3 subunits, including eIF3F. Additionally, depletion of eIF3F from GBM cells decreased the levels of PDCD4 protein. We also showed that PDCD4 and eIF3F directly interact with Bcl-xL RNA independently of each other. By performing IRES reporter, polysome profiling assays and EMSA we have demonstrated that eIF3F regulates IRES-mediated translation of Bcl-xL mRNA, likely via its interaction with PDCD4. - Source: PubMed
Publication date: 2026/04/29
Hegde VedaSharma Divya KPatel HarshilNarasimha Pavan LakshmiLuddu JasonMubaya RebeccaHolcik MartinThakor Nehal - Eukaryotic translation initiation factor 3 (eIF3) is a multi-subunit complex that promotes ribosome recruitment and messenger RNA (mRNA) selection. Here, we show that its eIF3g subunit, along with the binding partner eIF3i, mediates transcript-specific translation under mild heat stress through direct RNA binding. First, SELEX experiments identified a short GUCG-centered motif preferentially recognized by eIF3g, suggesting a sequence-specific binding preference. Next, ribosome profiling of yeast eIF3i mutant revealed that mRNAs containing GUCG motifs in their 5' coding regions exhibit elevated ribosome occupancy in a manner dependent on eIF3g/eIF3i module. A subset of SELEX-identified motifs, collectively termed the GUCG box, was found enriched in the 5'-terminal coding region of the regulated mRNAs. Reporter assays confirmed that these 5'-terminal coding regions are sufficient to drive heat-induced translation. Mutational analyses and biolayer interferometry demonstrated that disruption of the GUCG motif impairs eIF3g binding and diminishes translational induction. Moreover, GUCG motifs are periodically distributed across coding sequences and enriched near start codons, consistent with their role in stabilizing initiating ribosomes. Overall, this study establishes the GUCG box as a bona fide eIF3g-binding motif and validates its functional importance in vivo. These findings provide new insight into how eIF3 mediates stress-adaptive translation through sequence-specific RNA recognition. - Source: PubMed
Kato HiroakiOguro AkihiroMao YuanhuiOchsner KinsleyCasey HaileySakai GraceWan JiUsuki ShingoTang LeimingAsano MizukiBardiya NirmalaKaufman KadeIshiguro SusumuTani NaokiKumagai KazuyukiNakamura AkiraSingh Chingakham RanjitSakamoto TaiichiObayashi EijiQian Shu-BingAsano Katsura - Eukaryotic Initiation Factor 4 (eIF4) is a group of factors that activates mRNA for translation and recruit 43S preinitiation complex (PIC) to the mRNA 5' end, forming the 48S PIC. The eIF4 factors include mRNA 5' cap-binding protein eIF4E, ATP-dependent RNA helicase eIF4A, and scaffold protein eIF4G, which anchors eIF4A and eIF4E. Another eIF4 factor, eIF4B, stimulates the RNA helicase activity of eIF4A and facilitates mRNA recruitment. However, the mechanisms by which eIF4B binds the 40S ribosomal subunit and promotes mRNA recruitment remain poorly understood. Using cryo-Eletron Microscopy (cryo-EM), we obtained a map of the yeast 40S ribosomal subunit in a complex with eIF4B (40S-eIF4B complex). An extra density, tentatively assigned to yeast eIF4B, was observed near the mRNA entry channel of the 40S, contacting ribosomal proteins uS10, uS3, and eS10 as well as rRNA helix h16. Predictive modeling of the 40S-eIF4B complex suggests that the N-terminal domain of eIF4B binds near the mRNA entry channel, overlapping with the extra density observed in the 40S-eIF4B map. The partially open conformation of 40S in the 40S-eIF4B map is incompatible with eIF3j binding observed in the 48S PIC. Additionally, the extra density at the mRNA entry channel poses steric hindrance for eIF3g binding in the 48S PIC. Thus, structural insights suggest that eIF4B facilitates the release of eIF3j and the relocation of the eIF3b-g-i module during mRNA recruitment, thereby advancing our understanding of eIF4B's role in translation initiation. - Source: PubMed
Publication date: 2025/01/23
Datey AyushiSharma PraffulKhaja Faisal TariqueRahil HumaHussain Tanweer - During eukaryotic translation initiation, the small (40S) ribosomal subunit is recruited to the 5' cap and subsequently scans the 5' untranslated region (5' UTR) of mRNA in search of the start codon. The molecular mechanism of mRNA scanning remains unclear. Here, using GFP reporters in cells, we show that order-of-magnitude variations in the lengths of unstructured 5' UTRs have a modest effect on protein synthesis. These observations indicate that mRNA scanning is not rate limiting in yeast cells. Conversely, the presence of secondary structures in the 5' UTR strongly inhibits translation. Loss-of-function mutations in translational RNA helicases eIF4A and Ded1, as well as mutations in other initiation factors implicated in mRNA scanning, namely eIF4G, eIF4B, eIF3g and eIF3i, produced a similar decrease in translation of GFP reporters with short and long unstructured 5' UTRs. As expected, mutations in Ded1, eIF4B and eIF3i severely diminished translation of the reporters with structured 5' UTRs. Evidently, while RNA helicases eIF4A and Ded1 facilitate 40S recruitment and secondary structure unwinding, they are not rate-limiting for the 40S movement along the 5' UTR. Hence, our data indicate that, instead of helicase-driven translocation, one-dimensional diffusion predominately drives mRNA scanning by the 40S subunits in yeast cells. - Source: PubMed
Publication date: 2025/01/04
Wakabayashi HironaoZhu MingyiGrayhack Elizabeth JMathews David HErmolenko Dmitri N