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Jae-Hoon Jeong

Publications and source records attributed to Jae-Hoon Jeong.

10 recordsLinked to original sources
PubMed2006

ATR, PML, and CHK2 play a role in arsenic trioxide-induced apoptosis.

Arsenic trioxide (ATO) is a potent anti-leukemic chemotherapeutic agent for acute promyelocytic leukemia (APL) that results from a t (15, 17) chromosomal translocation that produces PML-RARalpha, a fusion protein between a tumor suppressor PML and the retinoic acid receptor RARalpha. APL patients are initially treated with retinoic acid, but most develop resistance and relapse. In contrast, ATO induces prolonged remissions even in the relapsed cases. However, the molecular mechanisms by which ATO kills the leukemic cells are not fully understood. We find that ATO induces apoptosis, at least in part, by activating proapoptotic kinase Chk2. ATO does this by stimulating ATR (ataxia telangiectasia mutated and Rad3-related) kinase, a Chk2-activating kinase. In conjunction, ATO degrades PML-RARalpha, resulting in the restoration of PML, which is required for autophosphorylation and full activation of Chk2. As a result, the p53-dependent apoptosis pathway is activated. Based on this, we propose that a pathway composed of ATR, PML, Chk2, and p53 plays a role in ATO-mediated apoptosis, a notion that is consistent with the observation that Chk2 is genetically intact and mutations in the p53 gene are extremely rare in APL.

Animals↗
PubMed2006

Promyelocytic leukemia activates Chk2 by mediating Chk2 autophosphorylation.

Chk2 is a kinase critical for DNA damage-induced apoptosis and is considered a tumor suppressor. Chk2 is essential for p53 transcriptional and apoptotic activities. Although mutations of p53 are present in more than half of all tumors, mutations of Chk2 in cancers are rare, suggesting that Chk2 may be inactivated by unknown alternative mechanisms. Here we elucidate one such alternative mechanism regulated by PML (promyelocytic leukemia) that is involved in acute promyelocytic leukemia (APL). Although p53-inactivating mutations are extremely rare in APL, t(15;17) chromosomal translocation which fuses retinoic acid receptor (RARalpha) to PML is almost always present in APL, while the other PML allele is intact. We demonstrate that PML interacts with Chk2 and activates Chk2 by mediating its autophosphorylation step, an essential step for Chk2 activity that occurs after phosphorylation by the upstream kinase ATM (ataxia telangiectasia-mutated). PML/RARalpha in APL suppresses Chk2 by dominantly inhibiting the auto-phosphorylation step, but inactivation of PML/RARalpha with alltrans retinoic acid (ATRA) restores Chk2 autophosphorylation and activity. Thus, by fusing PML with RARalpha, the APL cells appear to have achieved functional suppression of Chk2 compromising the Chk2-p53 apoptotic pathway.

Animals↗
PubMed2005

Inactivation of homocitrate synthase causes lysine auxotrophy in copper/zinc-containing superoxide dismutase-deficient yeast Schizosaccharomyces pombe.

The fission yeast Schizosaccharomyces pombe lacking copper/zinc-containing superoxide dismutase (CuZn-SOD) is auxotrophic for lysine and sulfurous amino acids under aerobic growth conditions. A multicopy suppressor gene (phx1+) that restored the growth of CuZn-SOD-deficient cells on minimal medium was isolated. It encodes a putative DNA-binding protein with a conserved homeobox domain. Overproduction of Phx1 increased the amount of several proteins, and one of those turned out to be a putative homocitrate synthase (HCS) encoded by the lys4+ gene in S. pombe as judged by mass spectrometric analysis. Consistent with this observation, overexpression of the lys4+ gene increased HCS enzyme activity and was sufficient to suppress the lysine requirement of the CuZn-SOD-deficient cells. Enzyme activity and Western blot analyses revealed that the activity and protein level of HCS were dramatically reduced upon depletion of CuZn-SOD. Treatment of exponentially growing S. pombe cells with paraquat, a superoxide generator, caused a decrease in the amount of Lys4 protein as expected. These results led us to conclude that HCS, the first enzyme in the alpha-aminoadipate-mediated pathway for lysine synthesis common in fungi and some bacteria, is a labile target of oxidative stress caused by CuZn-SOD depletion and that its synthesis is positively regulated by the putative transcriptional regulator Phx1.

Blotting, Northern↗
PubMed2005

Biomechanical comparisons of three different tibial tunnel directions in posterior cruciate ligament reconstruction.

PURPOSE: To investigate the effects of 3 different tunnel directions on the outcomes of posterior cruciate ligament (PCL) reconstruction surgery based on the forces exerted on the replacement ligament from a biomechanical point of view. The 3 tunnel directions in the proximal tibia are medial, central, and lateral. TYPE OF STUDY: Biomechanical study. METHODS: The forces exerted on the replaced PCL were calculated using finite element analyses as well as measurements from 6 cadavers. The results of the 3 surgical approaches were then compared. In the finite element analyses, the replaced ligament was assumed to have nonlinear elastic as well as viscoelastic properties. To simulate the overload in exercise, the femur was forced to move in the anterior direction abruptly while the tibia was held. From numerical analyses, the resultant forces, von Mises stresses, and maximum shear stresses on the replacement PCLs were calculated and compared. In the cadaveric study, a pressure-sensitive thin film was inserted between the replacement PCL and the killer turn area of the tibia. The color changes in films were evaluated using digital image processing in each case. RESULTS: The medial approach showed remarkably higher stresses and forces on the interface between the replaced PCL and the killer turn in both the numerical and cadaveric study. In contrast, the lateral approach showed the lowest stresses. CONCLUSIONS: The numerical and cadaveric studies indicate that the lateral approach is highly promising compared with the other approaches. CLINICAL RELEVANCE: The lateral approach has been shown to minimize stress concentration around the killer turn during in vitro experiments and a computer simulation of PCL reconstruction for long-term stability. The lateral approach technique appears to provide a promising clinical outcome in patients undergoing PCL reconstruction.

Arthroscopy↗
PubMed2004

Human T-cell leukemia virus type 1 Tax interacts with Chk1 and attenuates DNA-damage induced G2 arrest mediated by Chk1.

Checkpoint kinase 1 (Chk1) mediates diverse cellular responses to genotoxic stress, regulating the network of genome-surveillance pathways that coordinate cell cycle progression with DNA repair. Chk1 is essential for mammalian development and viability, and has been shown to be important for both S and G(2) checkpoints. We now present evidence that the HTLV-1 Tax protein interacts directly with Chk1 and impairs its kinase activities in vitro and in vivo. The direct and physical interaction of Chk1 and Tax was observed in HTLV-1-infected T cells (C81, HuT 102 and MT-2) and transfected fibroblasts (293 T) by coimmunoprecipitation and by in vitro GST pull-down assays. Interestingly, Tax inhibited the kinase activity of Chk1 protein in in vitro and in vivo kinase assays. Consistent with these results, Tax inhibited the phosphorylation-dependent degradation of Cdc25A and G(2) arrest in response to gamma-irradiation (IR) in a dose-dependent manner in vivo. The G(2) arrest did not require Chk2 or p53. These studies provide the first example of a viral transforming protein targeting Chk1 and provide important insights into checkpoint pathway regulation.

Cell Transformation, Viral↗
PubMed2003

Synovial chondromatosis in the quadriceps tendon.

We present a case of synovial chondromatosis originating from the quadriceps tendon sheath, which caused a complete quadriceps tendon rupture. The patient was treated using marginal excision. The ruptured quadriceps tendon was repaired. This is the first description of a quadriceps tendon rupture associated with synovial chondromatosis.

Adolescent↗
PubMed2003

Transarticular approach for elbow arthroscopy.

Arthroscopy of the stiff elbow joint is a technically difficult procedure because of the decreased joint space of the elbow joint, even to experienced surgeons. Problems encountered include limited access of instrument to the intra-articular space and an increased risk of cartilage injury in the contracted elbow joint. This study describes a novel transarticular approach for elbow arthroscopy that allows the safe and effective creation of the proximal medial and lateral portals.

Arthroscopy↗
PubMed2003

Synovitic cyclops syndrome caused by a Kennedy ligament augmentation device.

The cyclops lesion at the tibial attachment of the reconstructed ligament has been known to cause loss of knee extension. We present a case of knee extension loss because of a cyclops lesion caused by Kennedy ligament augmentation device synovitis at 10 years after ACL reconstruction in a 33-year-old man.

Accidental Falls↗
PubMedDate not supplied

Posterolateral rotatory instability treated by a modified biceps rerouting technique: technical considerations and results in cases with and without posterior cruciate ligament insufficiency.

PURPOSE: This study compared the clinical results of modified biceps femoris tenodesis with posterolateral rotatory instability (PLRI) injuries and PLRI combined with PCL injuries. TYPE OF STUDY: Case series. METHODS: Of 46 patients treated for PLRI, 21 had isolated PLRI (group 1), and 25 had PLRI with PCL injuries (group 2). The most common cause of injury was motor vehicle accident. The PCL was reconstructed using an arthroscopic 1-incision technique. The advantages of the modified Clancy technique include fixation of the biceps tendon to the isometric position and reduced surgical damage to the iliotibial band by dissection to the lateral femoral epicondyle through the interval between the iliotibial band and biceps muscle. RESULTS: All knees tested positive in the preoperative reverse pivot shift test, and 43 patients (93%) tested negative postoperatively. The side-to-side difference of an average external rotation thigh-foot angle (ERTFA) at both 30 degrees and 90 degrees of knee flexion was 15 degrees and 11 degrees in group 1 and 21 degrees and 26 degrees in group 2 preoperatively. Postoperative ERTFA tested at 30 degrees and 90 degrees of knee flexion were 10 degrees less than the uninvolved knee in both groups. At a mean follow-up of 40.3 months, the postoperative Lysholm knee score was 93.6 in group 1 and 90.4 in group 2. The postoperative HSS mean value was 91.1 in group 1 and 87.9 in group 2. A correction loss of more than 5 degrees was found in 3 patients of group 1 and in 5 patients of group 2 at an average 12 months after surgery. In 5 of 8 patients, severe scar tissues were found at the insertion site of the biceps tendon to the fibula during surgery. These tissues were associated with damage of the involved structures at the time of injury. CONCLUSIONS: Based on our experience, we recommend the modified biceps tenodesis for the reconstruction of both PLRI injuries and PLRI combined with PCL injuries except in patients with severe damage at the attachment site of the biceps tendon.

Adolescent↗