Psychiatry related information on Phf1

• Caspase-3-mediated cleavage of PHF-1 tau during apoptosis irrespective of excitotoxicity and oxidative stress: an implication to Alzheimer's disease [1].

High impact information on Phf1

• A PHD finger motif in the C terminus of RAG2 modulates recombination activity [2].
• Immunoblot analysis using anti-phospho-tau antibodies (AT-8, AT-100, AT-180, AT-270, PHF-1, and SMI-31) demonstrates the site-specific phosphorylation of tau at Ser-199, Ser-202, Ser-212, and Thr-214 in the brains of aged NPC1+/- mice [3].
• Functional analysis of disease and phosphoinositide-binding mutations reveals novel intramolecular interactions within the non-core region and suggests that the PHD finger adopts two distinct states [2].
• Immunoblot analysis using anti-tau antibodies (Tau-1, PHF-1, AT-180, and AT-100) revealed site-specific phosphorylation of tau at Ser-396 and Ser-404 in the brains of NPC homozygous mice [4].
• Morphological examination demonstrated that a number of neurons, the perikarya of which strongly immunostained with PHF-1, exhibited polymorphorous cytoplasmic inclusion bodies and multi-concentric lamellar-like bodies [4].

Biological context of Phf1

• Tctex3 showing restricted expression in male germ cells has been isolated during the process of chromosome walking in the mouse t-complex region [5].
• Ing1 belongs to the family of evolutionary conserved genes encoding nuclear PHD finger-containing proteins implicated in a variety of processes, including tumorigenesis, replicative senescence, excision repair and response to genotoxic stress [6].
• Cleavage form of PHF-1 tau was not observed in cortical cell cultures exposed to excitotoxins or oxidative stress that cause neuronal cell necrosis [1].
• The current findings suggest that PHF-1 tau is cleaved by caspase-3 during apoptosis and neurodegenerative process in AD [1].
• Similarly to the RING finger, the PHD finger is encoded by two exons [7].

Anatomical context of Phf1

• In the spinal cord, 87% of PHF-1-labeled cells colocalize with the transglutaminase-catalyzed cross-link [8].

Associations of Phf1 with chemical compounds

• Included in the group of the putative AF-2 TIFs identified so far is TIF1alpha, a member of a new family of proteins which contains an N-terminal RBCC (RING finger-B boxes-coiled coil) motif and a C-terminal bromodomain preceded by a PHD finger [9].
• Three discrete domains can be identified in the Xenopus laevis WSTF protein, a PHD finger, a DDT domain and a bromodomain [10].
• We demonstrate herein that dietary deprivation of folate and vitamin E, coupled with iron as a pro-oxidant, fosters an increase in nonphospho- and-phospho-tau within brain tissue of mice homozygously lacking apolipoprotein E as assayed by monoclonal antibodies Tau-1 and PHF-1, respectively [11].
• These studies describe a novel mechanism for MPTP neurotoxicity, namely a MPTP-inducible, strictly alpha-Syn-dependent, increased formation of PHF-1-reactive Tau, suggesting convergent overlapping pathways in the genesis of clinically divergent diseases such as AD and PD [12].

Other interactions of Phf1

• Mouse Tctex3 gene was mapped adjacent to Tsc2 gene on mouse Chromosome (Chr) 17, and HUTEX3 was located closely to HSET gene in the HLA class II region of chromosome 6 [5].
• The region containing this conserved motif is shared among members of the Polycomblike proteins that include the mouse M96 and Drosophila Polycomblike [5].
• An active fragment of caspase-3, a downstream mediator of cytochrome c, was observed within 8 h and cleaved PHF-1-positive tau [13].
• Alkaline phosphatase treatment abolished AT8 and PHF-1 immunoreactivity, confirming that the tau phosphorylation sites were at least at Ser(199/202) and Ser396 [14].
• When DVL-1 protein was overexpressed, the hyperphosphorylation of neurofilament at SMI31 and SMI32 epitopes and tau at PHF-1 (Ser-396/404), M4 (Thr-231/Ser-235), and Tau-1 (Ser-198/199/202) epitopes was attenuated [15].

Analytical, diagnostic and therapeutic context of Phf1

• PHF-1 tau was cleaved within 8 h following exposure of cortical cell cultures to apoptosis-inducing agents [1].
• By quantitative immunocytochemistry, we show that aberrant phosphorylation at the Ser199/Ser202 epitope (AT-8) and at the Ser 396 epitope (PHF-1) are moderately induced, proportionally to the degree of kinase stimulation [16].
• After 4 hr, cultures were fixed and processed for immunofluorescence with monoclonal antibodies (PHF-1, ALZ-50, Tau-1, AT8) directed against tau in various phosphorylation states followed by fluorescein-conjugated secondary antibodies [17].
• Microdensitometric analyses indicated that microinjection of PKC did not increase basal immunofluorescent intensities of the antibodies; by contrast, microinjection of PKM induced three- and twofold increases in PHF-1 and ALZ-50 levels, respectively [17].

References