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Biomedical subjects

Hongyuan Li

Publications and source records attributed to Hongyuan Li.

6 recordsLinked to original sources

Sequential phosphorylation and multisite interactions characterize specific target recognition by the FHA domain of Ki67.

The forkhead-associated (FHA) domain of human Ki67 interacts with the human nucleolar protein hNIFK, recognizing a 44-residue fragment, hNIFK226-269, phosphorylated at Thr234. Here we show that high-affinity binding requires sequential phosphorylation by two kinases, CDK1 and GSK3, yielding pThr238, pThr234 and pSer230. We have determined the solution structure of Ki67FHA in complex with the triply phosphorylated peptide hNIFK226-269(3P), revealing not only local recognition of pThr234 but also the extension of the beta-sheet of the FHA domain by the addition of a beta-strand of hNIFK. The structure of an FHA domain in complex with a biologically relevant binding partner provides insights into ligand specificity and potentially links the cancer marker protein Ki67 to a signaling pathway associated with cell fate specification.

CDC2 Protein Kinase↗

[Effects of eutrophication on distribution and population density of Corbicula fluminea and Bellamya sp. in Chaohu Lake].

The investigation on the distribution an d population density of C. fluminea and Bellamya sp. in Chaohu Lake during September 2001 and September 2002 showed that in the west region of the lake where was seriously eutrophic, the density and biomass of C. fluminea were 5.1 ind. x m(-2) and 17.87 g x m(-2) in 2001, and 8.8 ind. x m(-2) and 47.29 g x m(-2) in 2002, while those of Bellamya sp. were 13.3 ind. x m(-2) and 45.45 g x m(-2) in 2001, and 3.8 ind. x m(-2) and 12.56 g x m(-2) in 2002, respectively. In the east region of the lake where was eutrophic, the density and biomass of C. fluminea were 23.8 ind. x m(-2) and 67.86 g x m(-2) in 2001, and 29.2 ind. x m(-2) and 96.18 g x m(-2) in 2002, while those of Bellamya sp. were 10.1 ind. x m(-2) and 32.00 g x m(-2) in 2001, and 9.4 ind. x m(-2) and 31.21 g x m(-2) in 2002, respectively. The density and biomass of C. fluminea and Bellamya sp. were declined with increasing eutrophication. In hypertrophic region, C. fluminea and Bellamya sp. were absent. The density and biomass of the two species were obviously higher in littoral than in pelagic region. The distribution type of C. fluminea was core-model, while that of Bellamya sp. was random. The correlation between the density and biomass of C. fluminea and Bellamya sp. and water depth was not significant (P > 0.05). The biomass of Bellamya sp. was negatively correlated with water TN (P < 0.01), NO3-N (P < 0.05), TP(P < 0.01) and PO4-P (P < 0.05), while that of C. fluminea only had a significantly negative correlation with PO4-P(P < 0.05). Compared with 1981, there was fewer C. fluminea in the lake nowadays. The effects of other environmental factors on the population distribution and growth of C. fluminea and Bellamya sp. were also discussed.

Animals↗

Structure of human Ki67 FHA domain and its binding to a phosphoprotein fragment from hNIFK reveal unique recognition sites and new views to the structural basis of FHA domain functions.

Recent studies by use of short phosphopeptides showed that forkhead-associated (FHA) domains recognize pTXX(D/I/L) motifs. Solution structures and crystal structures of several different FHA domains and their complexes with short phosphopeptides have been reported by several groups. We now report the solution structure of the FHA domain of human Ki67, a large nuclear protein associated with the cell-cycle. Using fragments of its binding partner hNIFK, we show that Ki67-hNIFK binding involves ca 44 residues without a pTXX(D/I/L) motif. The pThr site of hNIFK recognized by Ki67 FHA is pThr234-Pro235, a motif also recognized by the proline isomerase Pin1. Heteronuclear single quantum coherence (HSQC) NMR was then used to map out the binding surface, and structural analyses were used to identify key binding residues of Ki67 FHA. The results represent the first structural characterization of the complex of an FHA domain with a biologically relevant target protein fragment. Detailed analyses of the results led us to propose that three major factors control the interaction of FHA with its target protein: the pT residue, +1 to +3 residues, and an extended binding surface, and that variation in the three factors is the likely cause of the great diversity in the function and specificity of FHA domains from different sources.

Binding Sites↗

[The anti-respiratory syncytial virus (RSV) effect of Radix Glycyrrhizae in vitro].

OBJECTIVE: To develop safe and effective anti-RSV new medicine from Radix Glycyrrhizae. METHOD: The anti-RSV effect of Radix Glycyrrhizae in Hela cell culture was observed by means of the inhibition of cytopathic effect. RESULT: In Hela cell culture, Radix Glycyrrhizae was found to be a inhibitor of RSV in a concentration-dependent manner. The median toxic concentration (TC50) of Radix Glycyrrhizae was 3.43 g/L, the median effective concentration (EC50) of Radix glycyrrhizae against replication of the Long strain of RSV in Hela cells were 0.2535 g/L, the selectivity index (TI = TC50/EC50) is 13.53. In time of addition experiment, Radix Glycyrrhizae inhibited the effect of RSV in Hela cells when it was added at 0 h, 2 h, 4 h, 6 h, 8 h after virus infection. CONCLUSION: In Hela cell culture, Radix Glycyrrhizae was found to be a inhibitor of RSV, there are many ways in the mechanisms.

Antiviral Agents↗

Direct binding of the N-terminus of HTLV-1 tax oncoprotein to cyclin-dependent kinase 4 is a dominant path to stimulate the kinase activity.

The involvement of Tax oncoprotein in the INK4-CDK4/6-Rb pathway has been regarded as a key factor for immortalization and transformation of human T-cell leukemia virus 1 (HTLV-1) infected cells. In both p16 -/- and +/+ cells, expression of Tax has been correlated with an increase in CDK4 activity, which subsequently increases the phosphorylation of Rb and drives the infected cells into cell cycle progression. In relation to these effects, Tax has been shown to interact with two components of the INK4-CDK4/6-Rb pathway, p16 and cyclin D(s). While Tax competes with CDK4 for p16 binding, thus suppressing p16 inhibition of CDK4, Tax also binds to cyclin D(s) with concomitant increases in both CDK4 activity and the phosphorylation of cyclin D(s). Here we show that both Tax and residues 1-40 of the N-terminus of Tax, Tax40N, bind to and activate CDK4 in vitro. In the presence of INK4 proteins, binding of Tax and Tax40N to CDK4 counteracts against the inhibition of p16 and p18 and acts as the major path to regulate Tax-mediated activation of CDK4. We also report that Tax40N retains the transactivation ability. These results of in vitro studies demonstrate a potentially novel, p16-independent route to regulate CDK4 activity by the Tax oncoprotein in HTLV-1 infected cells.

Amino Acid Motifs↗

[Effects of curcumin on proliferation and apoptosis in human hepatic cells].

OBJECTIVE: To investigate the effect of curcumin on the proliferation, cell cycle distribution and apoptosis of hepatocarcinoma cell line QGY. METHODS: The MTT method was used to assay the biologic activities of curcumin in different times and different doses. The cell cycle distribution was detected by flow cytometic analysis. The cell ultrastructure was observed by electronic microscopy. RESULTS: Curcumin could inhibit effectively QGY in a dose- and time- dependent manner. IC(50) of curcumin to QGY was 49.50 micromol/L in 72 hours. The cell growth was arrested at S stage. Curcumin could lead to the degeneration, necrosis, and apoptosis. CONCLUSIONS: Curcumin can interrupt the cell cycle and has a role in cytotoxicity, antiproliferation and inducing apoptosis of QGY.

Antineoplastic Agents↗