- olin kerännyt automaattista tietoa myös tästä, muta kun nobelin palkinto otti esiin HIF- tekijän säätelyn , tämäkin proteiiniryhmä heräsi toisella tavalla eloon minulle. Hypoksia stabiloi HIF1alfa lropyylihydroksylaatiolla lähinnä ja siinä on mm ZMYND mukana sinkkisormiryhmistäkin. Mutta HIFmRNA- säätelyssä on CPEB-ZZ ryhmää mukana. neuronaalisella aktivaatiolla on myös vaikutusta CPEB_ZZ struktuurinmuutoksessa, joka vaikuttaa HIF1a mRNA:n vapautumiseen ja pääsyyn ribosomille. Näyttää siltä että sekä CPEB1 ja CPEB2 molemmat osallistuvat HIF translaation toteutumisen säätelyyn sekventiaalisesti.
- Conserved Domains (4) summary
-
- cd12723
Location:234 → 341 - RRM1_CPEB1; RNA recognition motif 1 in cytoplasmic polyadenylation element-binding protein 1 (CPEB-1) and similar proteins
- cd12725
Location:352 → 437 - RRM2_CPEB1; RNA recognition motif 2 in cytoplasmic polyadenylation element-binding protein 1 (CPEB-1) and similar proteins
- pfam16366
Location:429 → 484 - CEBP_ZZ; Cytoplasmic polyadenylation element-binding protein ZZ domain
- pfam16368
Location:1 → 232 - CEBP1_N; Cytoplasmic polyadenylation element-binding protein 1 N-terminus
- cd12723
https://www.ncbi.nlm.nih.gov/Structure/cdd/cddsrv.cgi?uid=318563
Tämä on ainoa ryhmänsä edustaja ja osallistuu fysioliogisen prionisäikkeen muodostumiseen, jota pitkäaikaismuistin lataus tarvitsee. Siksi sanonkin tuota sinnkisormiproteiinin prionia zipriksi ti ziproniksi, koska se voi ehkä olla reversibeli prioni.
Olin etsimässä CEB1, CEB2 ja CEB3 proteiineja ensin varsinaisesta ZZZ joukosta ja välillä ZFAND joukosta koska havaitsin siinä tällaisia rakenteita (aa429-484) aminohapposekvenssissä ja koetin asettaa proteiieja noihin ryhmiin, mutta domeenia merkitäänkin CEB_ZZ nimellä ja se kuuluu CEBP-ZZ- perheeseen ainutlaatuisena ryhmänään.
kopion vihkoon rakennetta, merkkaan näkyviin cysteiinin C, Histidiinin H ja lisäksi Seriinin S.
/xxxxxxxxxxxCHxCSSxxxxxxCxxxxCxxxxCxxCHxxHSxxxxHHxxxxxx/
https://www.ncbi.nlm.nih.gov/Structure/cdd/cddsrv.cgi?uid=318563
Cytoplasmic polyadenylation element-binding protein ZZ domain
This ZZ-type zinc finger domain binds zinc via two conserved histidines in the C-terminal part of the domain.Lisätietoa tästä HIF1alfa proteiinin mRNA:ta säätelevästä proteiinista.
- CPEB1(15q25.2)
- Official Symbol
- CPEB1provided by HGNC
- Official Full Name
- cytoplasmic polyadenylation element binding protein 1provided by HGNC
- Gene type
- protein coding
- Also known as
- CPEB; CPEB-1; h-CPEB; CPE-BP1; hCPEB-1
- Summary
- This gene encodes a member of the cytoplasmic polyadenylation element binding protein family (CPEB_ZZ family) . This highly conserved protein binds to a specific RNA sequence, called the cytoplasmic polyadenylation element, found in the 3' untranslated region of some mRNAs. The encoded protein functions in both the cytoplasm and the nucleus. It is involved in the regulation of mRNA translation, as well as processing of the 3' untranslated region, and may play a role in cell proliferation and tumorigenesis. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jan 2014]
- Expression
- Biased expression in testis (RPKM 19.2), brain (RPKM 6.3) and 8 other tissues See more
- Orthologs mouse all
-
- Conserved Domains (4) summary
-
- cd12723
Location:234 → 341 - RRM1_CPEB1; RNA recognition motif 1 in cytoplasmic polyadenylation element-binding protein 1 (CPEB-1) and similar proteins
- cd12725
Location:352 → 437 - RRM2_CPEB1; RNA recognition motif 2 in cytoplasmic polyadenylation element-binding protein 1 (CPEB-1) and similar proteins
- pfam16366
Location:429 → 484 - CEBP_ZZ; Cytoplasmic polyadenylation element-binding protein ZZ domain
- pfam16368
Location:1 → 232 - CEBP1_N; Cytoplasmic polyadenylation element-binding protein 1 N-terminus
- cd12723
-
- RNA-binding protein CPEB1 remodels host and viral RNA landscapes. Batra R, et al. Nat Struct Mol Biol, 2016 Dec. PMID 27775709, Free PMC Article
-
Energy landscapes of a mechanical prion and their implications for the molecular mechanism of long-term memory.
Chen M, et al. Proc Natl Acad Sci U S A, 2016 May 3. PMID 27091989, Free PMC ArticleAplysia cytoplasmic polyadenylation element binding (CPEB) protein, a translational regulator that recruits mRNAs and facilitates translation, has been shown to be a key component in the formation of long-term memory. Experimental data show that CPEB exists in at least a low-molecular weight coiled-coil oligomeric form and an amyloid fiber form involving the Q-rich domain (CPEB-Q). Using a coarse-grained energy landscape model, we predict the structures of the low-molecular weight oligomeric form and the dynamics of their transitions to the β-form. Up to the decamer, the oligomeric structures are predicted to be coiled coils. Free energy profiles confirm that the coiled coil is the most stable form for dimers and trimers. The structural transition from α to β is shown to be concentration dependent, with the transition barrier decreasing with increased concentration. We observe that a mechanical pulling force can facilitate the α-helix to β-sheet (α-to-β) transition by lowering the free energy barrier between the two forms. Interactome analysis of the CPEB protein suggests that its interactions with the cytoskeleton could provide the necessary mechanical force. We propose that, by exerting mechanical forces on CPEB oligomers, an active cytoskeleton can facilitate fiber formation. This mechanical catalysis makes possible a positive feedback loop that would help localize the formation of CPEB fibers to active synapse areas and mark those synapses for forming a long-term memory after the prion form is established. The functional role of the CPEB helical oligomers in this mechanism carries with it implications for targeting such species in neurodegenerative diseases.
Q-rich protein; long-term memory; mechanical prion; protein aggregation
- Specificity factors in cytoplasmic polyadenylation. Charlesworth A, et al. Wiley Interdiscip Rev RNA, 2013 Jul-Aug. PMID 23776146, Free PMC Article
- The C-terminal region of cytoplasmic polyadenylation element binding protein is a ZZ domain with potential for protein-protein interactions. Merkel DJ, et al. J Mol Biol, 2013 Jun 12. PMID 23500490 Cytoplasmic polyadenylation element binding protein (CPEB) provides temporal and spatial control of protein synthesis required for early development and neuronal synaptic plasticity. CPEB regulates protein expression by inhibiting polyadenylation of selected mRNA transcripts, which prevents binding of the ribosome for protein synthesis. Two RNA recognition motif domains and a C-terminal binuclear zinc-binding domain are required for mRNA binding, but the zinc-binding domain is not required for sequence-specific recognition of the targeted mRNA transcript. The structure and function of the zinc-binding domain of CPEB are unknown. The C-terminal region of CPEB may participate in assembly of the ribonucleoprotein complex that includes the scaffold protein, Symplekin, and the cleavage and polyadenylation specificity factor. Sumoylation of Symplekin is required for polyadenylation, and both cleavage and polyadenylation specificity factor and poly(A) polymerase are sumoylated. The foreshortened poly(A) tail is maintained by poly(A) ribonuclease, which associates with CPEB. While zinc-binding domains are renowned for nucleic acid recognition, binuclear zinc-binding structural motifs, such as LIM (Lin-11, Isl-1, Mec-3), RING (really interesting new gene), PHD (plant homeodomain) and ZZ (ZZ-type zinc finger) domains, participate in protein-protein interactions. Here, we report the solution structure of the C-terminal zinc-binding domain of CPEB1 (CPEB1-ZZ), which has a cross-braced zinc binding topology. The structural similarity to other ZZ domains suggests that the CPEB1-ZZ domain recruits sumoylated proteins during assembly of the ribonucleoprotein complex prior to mRNA export from the nucleus.
- Translational control of cell growth and malignancy by the CPEBs. D'Ambrogio A, et al. Nat Rev Cancer, 2013 Apr. PMID 23446545
Chen PJ, Huang YS.EMBO J. 2012 Feb 15;31(4):959-71. doi: 10.1038/emboj.2011.448. Epub 2011 Dec 9.Translation of mRNA into protein proceeds in three phases: initiation, elongation, and termination. Regulated translation allows the prompt production of selective proteins in response to physiological needs and is often controlled by sequence-specific RNA-binding proteins that function at initiation. Whether the elongation phase of translation can be modulated individually by trans-acting factors to synthesize polypeptides at variable rates remains to be determined. Here, we demonstrate that the RNA-binding protein, cytoplasmic polyadenylation element binding protein (CPEB)2, interacts with the elongation factor, eEF2, to reduce eEF2/ribosome-triggered GTP hydrolysis in vitro and slow down peptide elongation of CPEB2-bound RNA in vivo. The interaction of CPEB2 with eEF2 downregulates HIF-1α RNA translation under normoxic conditions; however, when cells encounter oxidative stress, CPEB2 dissociates from HIF-1α RNA, leading to rapid synthesis of HIF-1α for hypoxic adaptation. This study delineates the molecular mechanism of CPEB2-repressed translation and presents a unique model for controlling transcript-selective translation at elongation.Free PMC Article2.Masuda K, Abdelmohsen K, Gorospe M.J Cell Mol Med. 2009 Sep;13(9A):2759-69. doi: 10.1111/j.1582-4934.2009.00842.x. Epub 2009 Jul 6. Review.In cells responding to low oxygen levels, gene expression patterns are strongly influenced by post-transcriptional processes. RNA-binding proteins (RBPs) are pivotal regulators of gene expression in response to numerous stresses, including hypoxia. Here, we review the RBPs that modulate mRNA turnover and translation in response to hypoxic challenge. The RBPs HuR (human antigen R) and PTB (polypyrimidine tract-binding protein) associate with mRNAs encoding hypoxia-response proteins such as HIF-1alpha and VEGF mRNAs, enhance their expression after hypoxia and play a major role in establishing hypoxic gene expression patterns. Additional RBPs such as iron-response element-binding proteins (IRPs), cytoplasmic polyadenylation-element-binding proteins (CPEBs) and several heterogeneous nuclear ribonucleoproteins (hnRNPs) also bind to hypoxia-regulated transcripts and modulate the levels of the encoded proteins. We discuss the efficient regulation of hypoxic gene expression by RBPs and the mounting interest in targeting hypoxia-regulatory RBPs in diseases with aberrant hypoxic responsesFree PMC Article3.Hägele S, Kühn U, Böning M, Katschinski DM.Biochem J. 2009 Jan 1;417(1):235-46. doi: 10.1042/BJ20081353.The heterodimeric HIF (hypoxia-inducible factor)-1 is a transcriptional master regulator of several genes involved in mammalian oxygen homoeostasis. Besides the well described regulation of the HIF-1alpha subunit via hydroxylation-mediated protein stability in hypoxia, there are several indications of an additional translational control of the HIF-1alpha mRNA, especially after growth factor stimulation.We identified an interaction of CPEB (cytoplasmic polyadenylation-element-binding protein) 1 and CPEB2 with the 3'-UTR (untranslated region) of HIF-1alpha mRNA. Overexpression of CPEB1 and CPEB2 affected HIF-1alpha protein levels mediated by the 3'-UTR of HIF-1alpha mRNA. Stimulation of neuroblastoma SK-N-MC cells with insulin and thus activation of endogenous CPEBs increased the expression of a luciferase reporter gene fused to the 3'-UTR of HIF-1alpha as well as endogenous HIF-1alpha protein levels. This could be abrogated by treating the cells with CPEB1 or CPEB2 siRNAs (short interfering RNAs). Injection of HIF-1alpha cRNA into Xenopus oocytes verified the elongation of the poly(A)+ (polyadenylated) tail by cytoplasmic polyadenylation. Thus CPEB1 and CPEB2 are involved in the regulation of HIF-1alpha following insulin stimulation.Free ArticleHypoxian indusoiman tekijän HIF säätelystä.
Inga kommentarer:
Skicka en kommentar