ZFP sinkkiproteiinit Zf C3H -tyyppi

Tristetraprolin (TTP) and TTP-Like Proteins

The tristetraprolin family consists of three proteins with characteristic tandem zinc-finger domains, including TTP (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 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.

https://www.frontiersin.org/articles/10.3389/fnmol.2011.00007/full#B28