The Experts below are selected from a list of 171 Experts worldwide ranked by ideXlab platform
John Kuriyan - One of the best experts on this subject based on the ideXlab platform.
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structure of the c terminal region of P21waf1 cip1 complexed with human pcna
Cell, 1996Co-Authors: Jacqueline M Gulbis, Zvi Kelman, Jerard Hurwitz, Mike Odonnell, John KuriyanAbstract:The crystal structure of the human DNA polymerase delta processivity factor PCNA (proliferating cell nuclear antigen) complexed with a 22 residue peptide derived from the C-terminus of the cell-cycle checkpoint Protein P21(WAF1/CIP1) has been determined at 2.6 angstrom resolution. P21 binds to PCNA in a 1:1 stoichiometry with an extensive array of interactions that include the formation of a beta sheet with the interdomain connector loop of PCNA. An intact trimeric ring is maintained in the structure of the P21-PCNA complex, with a central hole available for DNA interaction. The ability of P21 to inhibit the action of PCNA is therefore likely to be due to its masking of elements on PCNA that are required for the binding of other components of the polymerase assembly.
Michael A. Simon - One of the best experts on this subject based on the ideXlab platform.
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an sh3 sh2 sh3 Protein is required for P21ras1 activation and binds to sevenless and sos Proteins in vitro
Cell, 1993Co-Authors: Michael A. SimonAbstract:Abstract Activation of the sevenless Protein-tyrosine kinase is required for the proper specification of R7 photoreceptors in the Drosophila eye. The activation of a Ras Protein, P21 Ras1 , is a crucial early event in the signaling pathway, and constitutive activation of P21 Ras1 is sufficient to induce all of the effects of sevenless action. Here we report that another gene, E(sev)2B , required for proper signaling by sevenless encodes a Protein of the structure SH3-SH2-SH3. We further provide evidence that the E(sev)2B Protein is required for activation of P21 Ras1 but not for any subsequent events, and that this Protein can bind in vitro to sevenless and to Son of sevenless (Sos), a putative guanine nucleotide exchange factor for P21 Ras1 . These results suggest that the E(sev)2B Protein may act to stimulate the ability of Sos to catalyze P21 Ras1 activation by linking sevenless and Sos in a signaling complex. We have renamed the E(sev)2B locus downstream of receptor kinases (drk) .
Mike Odonnell - One of the best experts on this subject based on the ideXlab platform.
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structure of the c terminal region of P21waf1 cip1 complexed with human pcna
Cell, 1996Co-Authors: Jacqueline M Gulbis, Zvi Kelman, Jerard Hurwitz, Mike Odonnell, John KuriyanAbstract:The crystal structure of the human DNA polymerase delta processivity factor PCNA (proliferating cell nuclear antigen) complexed with a 22 residue peptide derived from the C-terminus of the cell-cycle checkpoint Protein P21(WAF1/CIP1) has been determined at 2.6 angstrom resolution. P21 binds to PCNA in a 1:1 stoichiometry with an extensive array of interactions that include the formation of a beta sheet with the interdomain connector loop of PCNA. An intact trimeric ring is maintained in the structure of the P21-PCNA complex, with a central hole available for DNA interaction. The ability of P21 to inhibit the action of PCNA is therefore likely to be due to its masking of elements on PCNA that are required for the binding of other components of the polymerase assembly.
David Givol - One of the best experts on this subject based on the ideXlab platform.
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induction of waf1 cip1 by a p53 independent pathway
Cancer Research, 1994Co-Authors: Paolo Michieli, Marcio Chedid, D Lin, Jacalyn H Pierce, W E Mercer, David GivolAbstract:Abstract The p53-inducible gene WAF1/CIP1 encodes a M r 21,000 Protein (P21) that has been shown to arrest cell growth by inhibition of cyclin-dependent kinases. Induction of WAF1/CIP1 in cells undergoing p53-dependent G 1 arrest or apoptosis supports the idea that WAF1/CIP1 is a critical downstream effector of p53. In the present study, we used embryonic fibroblasts from p53 “knock-out” mice to demonstrate p53-independent induction of WAF1/CIP1 . We show that serum or individual growth factors such as platelet-derived growth factor, fibroblast growth factor, and epidermal growth factor but not insulin are able to induce WAF1/CIP1 in quiescent p53-deficient cells as well as in normal cells. The kinetics of this transient induction, which is enhanced by cycloheximide, demonstrates that WAF1/CIP1 is an immediate-early gene the transcript of which reaches a peak at approximately 2 h following serum or growth factor stimulation. On the other hand, DNA damage elicited by γ-irradiation induces WAF1/CIP1 in normal human and mouse fibroblasts but does not affect WAF1/CIP1 expression in p53-deficient cells. These results suggest the existence of two separate pathways for the induction of WAF1/CIP1 , a p53-dependent one activated by DNA damage and a p53-independent one activated by mitogens at the entry into the cell cycle. The possible function of P21 at this early stage is discussed.
Torsten E. Reichert - One of the best experts on this subject based on the ideXlab platform.
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The cell cycle regulator Protein P16 and the cellular senescence of dental follicle cells
Molecular and Cellular Biochemistry, 2017Co-Authors: Christian Morsczeck, Anja Reck, Markus Hullmann, Torsten E. ReichertAbstract:Cellular senescence is a restricting factor for regenerative therapies with somatic stem cells. We showed previously that the onset of cellular senescence inhibits the osteogenic differentiation in stem cells of the dental follicle (DFCs), although the mechanism remains elusive. Two different pathways are involved in the induction of the cellular senescence, which are driven either by the cell cycle Protein P21 or by the cell cycle Protein P16. In this study, we investigated the expression of cell cycle Proteins in DFCs after the induction of cellular senescence. The induction of cellular senescence was proved by an increased expression of β-galactosidase and an increased population doubling time after a prolonged cell culture. Cellular senescence regulated the expression of cell cycle Proteins. The expression of cell cycle Protein P16 was up-regulated, which correlates with the induction of cellular senescence markers in DFCs. However, the expression of cyclin-dependent kinases (CDK)2 and 4 and the expression of the cell cycle Protein P21 were successively decreased in DFCs. In conclusion, our data suggest that a P16-dependent pathway drives the induction of cellular senescence in DFCs.
