Disease relevance of HINT1

• PKCI-1 is a member of the HIT family of proteins, shown by sequence identity to be conserved in a broad range of organisms including mycoplasma, plants, and humans [1].
• Induction of endonuclease G-mediated apopotosis in human oral squamous cell carcinoma cells by protein kinase C inhibitor safingol [2].
• We investigated the cellular toxicity of FCCP in HL60 and CCRF-CEM cells alone or in combination with the known apoptosis inducers such as inhibitor of serine/threonine protein kinases staurosporine (Sts) and protein kinase C inhibitor chelerythrine [3].
• HIT family genes: FHIT but not PKCI-1/HINT produces altered transcripts in colorectal cancer [4].
• Furthermore, four adenomas and one adenocarcinoma of the glandular stomach were found in the NMBA-treated PKCI-/- mice but no tumors of the glandular stomach were found in the NMBA-treated PKCI+/+ mice or in any of the untreated mice [5].

Psychiatry related information on HINT1

• Aprataxin, a Hint branch hydrolase, is mutated in ataxia-oculomotor apraxia syndrome [6].

High impact information on HINT1

• Therefore, the paper by Lee et al. in this issue of Immunity that ascribes a role for the histidine triad protein HINT (also designated HINT1) in regulating the activity of the microphthalmia transcription factor (MITF) is of great interest [7].
• Adhesion was affected by a qualitative change in LFA-1 molecules and was reversed by the protein kinase C inhibitor sphingosine [8].
• We show that secretion of vimentin, which is phosphorylated at serine and threonine residues, is enhanced by the phosphatase inhibitor okadaic acid and blocked by the specific protein kinase C inhibitor GO6983 [9].
• This stimulated release was shown to be (a) concentration- and time-dependent, (b) partially blocked by the protein synthesis inhibitor cycloheximide, and (c) significantly inhibited by the protein kinase C inhibitor Ro-31,8220 [10].
• Upregulation by the B1-agonist was blocked by a specific protein kinase C inhibitor [11].

Chemical compound and disease context of HINT1

• Increased DNA synthesis of dermatofibrosarcoma protuberans cells was abolished by genistein, a tyrosine kinase inhibitor, or by PD98059, a specific extracellular signal related kinase pathway inhibitor, but not by calphostin C, a protein kinase C inhibitor [12].
• Protein kinase C inhibitor staurosporine, but not cyclic nucleotide-dependent protein kinase inhibitor HA-1004, also dramatically reduced constitutive levels of nuclear NF kappa B. Finally, TPA addition to monocytes infected with HIV-1 inhibited HIV-1 replication, as determined by reverse transcriptase assays, in a concentration-dependent manner [13].
• A protein kinase C inhibitor, staurosporin, significantly inhibited T cell binding to transfected melanoma cells, while cyclosporin A and wortmannin, an inhibitor of phosphatidylinositol-3-kinase, did not [14].
• OBJECTIVES: To determine if the protein kinase C inhibitor, H-7, alone can cause acute lung injury [15].
• Both the gene transfer of estrogen receptor alpha using adenovirus and treatment with the protein kinase C inhibitor bisindolylmaleimide I significantly enhanced the effects of 17beta-E2 treatment under high-glucose conditions, whereas these effects were abolished by the estrogen receptor antagonist ICI 182,780 (faslodex) [16].

Biological context of HINT1

• Gene expression levels for HINT1, MDH1, and SERPINI1 were significantly different between the groups [17].
• To identify other proteins that interact with hPKCI, in the present study, we used the hPKCI as a bait in the yeast two-hybrid system, together with a mouse embryo cDNA library [18].
• We suggest that the ATDC and hPKCI-1 proteins may be components of a signal transduction pathway that is induced by ionizing radiation and mediated by protein kinase C [19].
• The hPKCI-1 gene (HGMV-approved symbol PRKCNH1) maps to human chromosome 5q31.2 by fluorescence in situ hybridization [20].
• Hint/PKCI-1, which is the only other characterized human histidine triad (HIT) nucleotide-binding protein in addition to tumor-suppressor gene FHIT, might be involved in lung carcinogenesis [21].

Anatomical context of HINT1

• Northern blot analysis indicated that a 0.7-kb PKCI mRNA was expressed in several tissues obtained from adult mice and also in a variety of rodent and human cell lines [18].
• Microscopy of immunostained cells indicated that the PKCI protein was present mainly in the nucleus of both normal and tumor-derived epithelial cell lines [18].
• Indirect immunofluorescence shows that hPKCI-1 localizes to cytoskeletal structures in the cytoplasm of a human fibroblast cell line and is largely excluded from the nucleus [20].
• Effect of the protein kinase C inhibitor staurosporine on chemosensitivity to daunorubicin of normal and leukemic fresh myeloid cells [22].
• Contrasting actions of staurosporine, a protein kinase C inhibitor, on human neutrophils and primary mouse epidermal cells [23].

Associations of HINT1 with chemical compounds

• Crystal structures of nucleotide-bound forms of histidine triad nucleotide-binding protein (Hint) demonstrated that the conserved residues in HIT proteins are responsible for their distinctive, dimeric, 10-stranded half-barrel structures that form two identical purine nucleotide-binding sites [24].
• In addition, these teleocidin effects were not mimicked by the protein kinase C agonist 1-oleoyl-2-acetylglycerol or inhibited by the protein kinase C inhibitor 1-(5-isoquinolinylsulfonyl)-2-methylpiperazine [25].
• Here we show that rabbit and yeast Hint hydrolyze the natural product adenosine-5'-monophosphoramidate (AMPNH(2)) in an active-site-dependent manner at second order rates exceeding 1,000,000 m(-1) s(-1) [26].
• Furthermore, these Ang II effects were abolished by the protein kinase C inhibitor bisindolylmaleimide I and the MAPK inhibitor PD98059 [27].
• The present studies were conducted to determine if the morphological effect and the phosphorylation effect of PMA could be blocked by treatment with sphingosine, a protein kinase C inhibitor [28].

Enzymatic interactions of HINT1

• We also demonstrate that Aprataxin hydrolyzes with similar efficiency the model histidine triad nucleotide-binding protein substrate, AMPNH2, and the Fragile histidine triad protein substrate, Ap4A [29].

Regulatory relationships of HINT1

• The protein kinase C inhibitor GF 109203X partially inhibited PTH-induced apoptosis [30].
• IL-2-induced migration could also be prevented by the protein kinase C inhibitor H-7, but calcitriol appeared to be at least 1,000 times more potent [31].
• Additionally, Abeta-induced transendothelial migration of monocytes were inhibited by protein kinase C inhibitor and augmented by phosphatase inhibitor [32].
• The TRH-stimulated phospholipase C activity was not attenuated following pretreatment with 12-O-tetradecanoylphorbol 3-acetate (TPA) to stimulate protein kinase C activity, and TRH also induced desensitization in the presence of the protein kinase C inhibitor polymyxin B [33].
• Further studies established that the Ep-induced increase in beta-globin mRNA could be inhibited by the tyrosine kinase inhibitor genistein and the protein kinase C inhibitor Compound 3.(ABSTRACT TRUNCATED AT 250 WORDS)[34]

Other interactions of HINT1

• The male individuals with schizophrenia compared to male controls showed reductions by 2.8- to 3.7-fold of HINT1, neuroserpin, and MDH1 by Q-PCR [17].
• A structural comparison of FHIT with PKCI and galactose-1-phosphate uridylyltransferase (GaIT) reveals additional implications for the structural and functional evolution of the ubiquitous HIT family of proteins [35].
• The selective MAPKK inhibitor PD098059, the protein kinase C inhibitor K252a or the phospholipase C inhibitor U73122 did not significantly inhibit Ang II augmented 3H-leucine incorporation [36].
• Pretreatment of FSC with H-7, a protein kinase C inhibitor, blocked cytokine-induced increase in both MCP-1 gene expression and secretion [37].
• PTHrP (107-139) stimulation of mRNA and protein in hOB cells was abolished by bisindolylmaleimide I, a protein kinase C inhibitor, but not by either adenosine 3',5'-cyclic monophosphorothioate, Rp-isomer (Rp-cAMPS), or N-[2-((p-bromocinnamyl)amino)ethyl]-5-isoquinolinesulfonamide dihydrochloride (H89), two protein kinase A inhibitors [38].

Analytical, diagnostic and therapeutic context of HINT1

• Western blot analyses, using a polyclonal antibody prepared against hPKCI, indicated that this protein is expressed at relatively high levels in several murine tissues and in a variety of human cell lines prepared from normal tissues or tumors [18].
• The three-dimensional structure of protein kinase C interacting protein 1 (PKCI-1) has been solved to high resolution by x-ray crystallography using single isomorphous replacement with anomalous scattering [1].
• Electron microscopy shows that a protein kinase C inhibitor does not impair binding of HIV to CD4+ cells, but causes an apparent accumulation of virus particles at the cell surface, at the same time inhibiting viral infectivity [39].
• No prevention of ischemic preconditioning by the protein kinase C inhibitor staurosporine in swine [40].
• This interaction was initially observed in a yeast two-hybrid study and subsequently verified by co-immunoprecipitation and subcellular localization studies, where overexpression of Cdk7 leads to partial relocalization of Hint to the nucleus [41].

References