Mielenkiintoinen ryhmä. 38 geeniä. Eräs lähde sanoo: 35 geeni ja niistä 2 transkriptiotekijää. Linkistä sa nimet, synoyymit ja geenin sijainnin kromosomissa.
Näistä mainittiin ZFP36 seuraavassa yhteydessä:
Post-transcriptional control of the hypoxic response by RNA-binding proteins and microRNAs
ZFP36 (19q13.2) ; TTP , tristetraproliiniMuita nimiä: RNF162A, EGF response factor 1, NUP475,TIS11, Zfp-36, GOS24, RNA decay activator protein.
( Kun Nobelin palkinto tnä vuonna tuli hypoxian ja normoxian homeostaasia käsittelevästä asiasta, huomasin että usea sinkkiproteiinikin on tässä säätelyssä mukana.
Myös tästä sikkisormirakenteen C3H- omaavasta ryhmästä mainitaan tekijää).
Abstraktista sitaatti:
"Mammalian gene expression patterns change profoundly in response to low oxygen levels (HYPOXIA). These changes in gene expression programs are strongly influenced by post-transcriptional mechanisms mediated by mRNA-binding factors: RNA-binding proteins (RBPs) and microRNAs (miRNAs).
Here, we review the RBPs and miRNAs that modulate mRNA turnover and translation in response to hypoxic challenge.
RBPs such as HuR (human antigen R), PTB (polypyrimidine tract-binding protein), heterogeneous nuclear ribonucleoproteins (hnRNPs), tristetraprolin, ZFP36, Zf-C3H type) ), nucleolin, iron-response element-binding proteins (IRPs), and cytoplasmic polyadenylation-element-binding proteins (CPEBs), selectively bind to numerous hypoxia-regulated transcripts and play a major role in establishing hypoxic gene expression patterns. MiRNAs including miR-210, miR-373, and miR-21 associate with hypoxia-regulated transcripts and further modulate the levels of the encoded proteins to implement the hypoxic gene expression profile. We discuss the potent regulation of hypoxic gene expression by RBPs and miRNAs and their integrated actions in the cellular hypoxic response."
(Otan sitaatin myös kappaleesta jossa tämä ZFP36 mainitaan (TTP, tristetraproliini, RNA decay activating protein)
- MicroRNAs and several RBPs such as TTP can modulate mRNA stability in response to hypoxia.
- The tristetraprolin (TTP) family consists of three proteins with characteristic tandem zinc-finger domains, includingTTP (also known as zinc-finger protein 36, ZFP36),ZFP36L1 or TIS11B (tetradecanoylphorbol acetate-inducible sequence 11B),and ZFP36L2 or TIS11D.TTP is inducible by different stimuli, including hypoxia, is predominantly cytoplasmic, and promotes the decay of target mRNAs in a variety of systems (Carballo et al., 1998; Kim et al., 2010).TTP was found to interact with the HIF-1α 3′UTR and promoted the degradation of HIF-1α mRNA (Kim et al., 2010).The generally reduced levels of TTP in many cancers was further proposed to contribute to the increased HIF-1α levels seen in many cancers (Brennan et al., 2009; Kim et al., 2010).In macrophages, the joint presence of hypoxia and lipopolysaccharide (LPS) led to decreased tumor necrosis factor (TNF)-α mRNA stability and TNF-α production, as well as to the reduced half-life and steady-state levels of mRNAs encoding other proinflammatory cytokines [macrophage inflammatory protein 2 (MIP2), interleukin (IL)-6, and granulocyte macrophage colony-stimulating factor (GM-CSF)]. This reduction was due, at least in part, to the decreased activity of p38, a kinase that phosphorylates and thereby inactivates TTP in hypoxic, LPS-treated cells (Werno et al., 2010).Hypoxia also increased the levels of MKP-3 [the mitogen-activated protein (MAP) kinase phosphatase-3], a dual-specificity phosphatase for MAP kinases ERK1/2.As TTP associated with the MKP-3 3′UTR and lowered the stability of an MKP-3 3′UTR reporter transcript, MKP-3 upregulation was attributed to the reduced decay-promoting influence of TTP upon MKP-3 mRNA during hypoxia (Bermudez et al., 2011).The TTP-related protein TIS11B, RNF162B was found to interact with the 3′UTR of the VEGF mRNA and lowered VEGF mRNA stability (Ciais et al., 2004).Very recently, the levels of TIS11B were shown to be controlled by pVHL. In normoxic renal cell carcinoma (RCC) cells ectopically expressing pVHL, increased abundance of the microRNA hsa-miR-29b was responsible for decreasing TIS11B mRNA stability and TIS11B protein levels (Sinha et al., 2009). Hypoxia also increased TIS11B expression in pVHL-expressing RCC cells, although the specific mechanisms were not identified.
The overexpression of each of the three family members can suppress the expression of a HIF1α3′UTR reporter construct through the control of mRNA stability [92].
TTP family members bind to AU-rich elements within the UTRsof a variety of genes and endogenous TTP physically interacts with HIF1αmRNA as measured byRNA IP [92]. In the case of the HIF1α transcript, TTP can bind to a well-defined region in the 3′UTRof HIF1α and induce its degradation [91,92]. siRNA knock down experiments show that TTP can specifically destabilise HIF1α mRNA in cells exposed to prolonged hypoxia, but not normoxic cells,perhaps indicating that TTP plays a role in a hypoxia-specific HIF1 negative feedback loop [91,92].The m RNAs targeted by TTP encode protein products such as HIF1α, which are critical for the progression of several malignancies [95–98]. The loss of TTP has been reported in several human cancers; this correlates with the elevation of HIF1α and poor prognosis [95–98].6.5. RNA Binding Motif Protein 38RNA Binding Motif Protein 38 (RBM38) is an ad
TTP, tristetraproliini on DNA:n degradaatiota aktivoiva proteiini ja säätelee täten myös HIF1alfaa hypoksiasta riippuvalla tavalla.
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