High impact information on PIP2

• Current paradigms propose that PI(4)P acts primarily as a precursor to phosphatidylinositol 4,5 bisphosphate (PIP2), an important plasma membrane regulator [1].
• The responses of mammalian cells to external signals are commonly mediated by intracellular secondary messengers, among which are the breakdown products of phosphatidylinositol 4,5-bisphosphate (PIP2): 1,2-diacylglycerol (DG) and inositol 1,4,5-triphosphate (IP3) (refs 1-7) [2].
• Interactions with PIP2, ADP-actin monomers, and capping protein regulate the activity and localization of yeast twinfilin [3].
• A pip2 deletion strain is impaired in growth on oleate as sole carbon source and the induction of beta-oxidation enzymes is abolished [4].
• Pip2p: a transcriptional regulator of peroxisome proliferation in the yeast Saccharomyces cerevisiae [4].

Biological context of PIP2

• Electrophoretic mobility shift analysis demonstrated that Adr1p bound to UAS1PIP2, and Northern analysis in combination with a lacZ reporter gene confirmed that Adr1p influenced the transcription of PIP2 [5].
• In addition, diploids deleted at either PIP2 or OAF1 demonstrated abundant ascosporogenesis, indicating that these genes are not essential for sporulation [6].
• This up-regulation depended on the Pip2p-Oaf1p transcription factor and was accompanied by induction of import-competent peroxisomes [7].
• Pip2p and Oaf1p form an example of a heterodimere of yeast Zn2Cys6 zinc-finger proteins binding to DNA [8].
• By searching the S. cerevisiae genomic database for the consensus sequence that acts as a target for these transcription factors, we identified 40 genes that contain a putative Oaf1p-Pip2p binding site in their promoter region [9].

Anatomical context of PIP2

• These functions include cell-surface receptor-regulated hydrolysis of PIP2 by phospholipases C beta- and gamma-isozymes, regulated release of secretory granules, and the budding of constitutive secretory vesicles and immature secretory granules from the trans-Golgi network [10].
• Phosphatidylinositol 3,5-bisphosphate (PI(3,5)P2), a recently discovered PIP2 isomer, is ubiquitous in eukaryotic cells and rapidly accumulates in hyperosmotically stressed yeast [11].

Associations of PIP2 with chemical compounds

• The OAF1 gene was constitutively expressed, while the PIP2 gene was induced upon growth on oleate, giving rise to positive autoregulatory control [8].
• These protein interactions have defined requirements for phosphatidylinositol 4,5-bisphosphate (PIP2) [12].
• PIP2 also had the greatest effect on the rate of binding of guanosine 5'-(gamma-thio)triphosphate (GTP gamma S), increasing it almost 100-fold at early time points [12].
• We demonstrate that Oaf1p regulates certain genes in the absence of Pip2p and that both of these transcription factors play a role in maintaining the glucose-repressed state of one gene [9].
• Hydrolysis of phosphatidylinositol 4,5-bisphosphate (PIP2) by phosphatidylinositol-specific phospholipase C (PI-PLC) generates two second messengers, inositol 1,4,5-trisphosphate and 1,2-diacylglycerol [13].

Physical interactions of PIP2

• Studies based on lacZ reporter genes and in vitro protein-DNA interactions revealed that the PEX25 ORE could bind Pip2p-Oaf1p and confer activation on a basal promoter [14].
• We demonstrate that the induction of Oaf1/Pip2 activity by the fatty acid oleate depends on oleate's direct binding to the Oaf1 LBD [15].

Other interactions of PIP2

• In addition, the amount of Pip2p-Oaf1p that bound to a target ORE in vitro was reduced in mutant extracts compared with the wild-type [5].
• Regulation of the yeast SPS19 gene encoding peroxisomal 2,4-dienoyl-CoA reductase by the transcription factors Pip2p and Oaf1p: beta-oxidation is dispensable for Saccharomyces cerevisiae sporulation in acetate medium [6].
• However, regulation of ODC1 does not require the transcription factors Oaf1p and Pip2p, known to mediate oleic acid induction of other genes [16].
• UAS(SPS19), which is similar to a transcriptional enhancer in the promoter of the sporulation-specific gene SPS4, was shown specifically to bind several proteins, including Pip2p and Oaflp [17].
• The PEX25 promoter contains an oleate response element (ORE)-like sequence comprising a CGG palindrome lacking a canonical adenine, which is considered critical for element function and Pip2p-Oaf1p binding [14].

Analytical, diagnostic and therapeutic context of PIP2

• Immunoprecipitation showed that, in adr1delta mutant cells grown on oleic acid, Pip2p was less abundant compared with the corresponding wild-type [5].

References