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Dysregulated CREB3 cleavage at the nuclear membrane induces karyoptosis-mediated cell death
Lee Ga-Eun,Bang Geul,Byun Jiin,Lee Cheol-Jung,Chen Weidong,Jeung Dohyun,An Hyun-Jung,Kang Han Chang,Lee Joo Young,Lee Hye Suk,Hong Young-Soo,Kim Dae Joon,Keniry Megan,Kim Jin Young,Choi Jin-Sung,Fanto 생화학분자생물학회 2024 Experimental and molecular medicine Vol.56 No.-
Cancer cells often exhibit resistance to apoptotic cell death, but they may be vulnerable to other types of cell death. Elucidating additional mechanisms that govern cancer cell death is crucial for developing new therapies. Our research identified cyclic AMP-responsive element-binding protein 3 (CREB3) as a crucial regulator and initiator of a unique cell death mechanism known as karyoptosis. This process is characterized by nuclear shrinkage, deformation, and the loss of nuclear components following nuclear membrane rupture. We found that the N-terminal domain (aa 1-230) of full-length CREB3 (CREB3-FL), which is anchored to the nuclear inner membrane (INM), interacts with lamins and chromatin DNA. This interaction maintains a balance between the outward force exerted by tightly packed DNA and the inward constraining force, thereby preserving INM integrity. Under endoplasmic reticulum (ER) stress, aberrant cleavage of CREB3-FL at the INM leads to abnormal accumulation of the cleaved form of CREB3 (CREB3-CF). This accumulation disrupts the attachment of CREB3-FL to the INM, resulting in sudden rupture of the nuclear membrane and the onset of karyoptosis. Proteomic studies revealed that CREB3-CF overexpression induces a DNA damage response akin to that caused by UVB irradiation, which is associated with cellular senescence in cancer cells. These findings demonstrated that the dysregulation of CREB3-FL cleavage is a key factor in karyoptotic cell death. Consequently, these findings suggest new therapeutic strategies in cancer treatment that exploit the process of karyoptosis.
Han-Min Lee,Gil-Dong Kim,Kwang-Hae Oh,An-Ho Lee,Chen-Soo Ha 전력전자학회 2004 ICPE(ISPE)논문집 Vol.- No.-
Harmonic current originating from electric locomotives can be magnified due to the impedance characteristics of power supply circuit and bring about various problems. That is, electromagnetic interference with communication lines, operational trouble in signaling, overheat and/or vibration in po wer capacitor, malfunction in protection relay and so on. Therefore, the exact assessment of the harmonic current flow must be undertaken at designing and planning stage for the electric traction systems.<br/> For these reasons, we proposed a new approach to model and to analyze traction power feeding system focused on system response to current and voltage harmonic. Moreover, harmonic characteristics in electric train depend on its operational modes. Therefore, Measurements of harmonics are performed on the real railway power supply systems under normal operation. The spectrum and distortion analyses in measurement data are variously described in this study.
Chen, Xiaoqiang,Lee, Kyung-Ah,Ha, Eun-Mi,Lee, Kyung Mi,Seo, You Yeong,Choi, Han Kyoung,Kim, Ha Na,Kim, Min Jung,Cho, Chun-Seok,Lee, Soo Young,Lee, Won-Jae,Yoon, Juyoung Royal Society of Chemistry 2011 Chemical communications Vol.47 No.15
<P>A specific and sensitive fluorescence-based method was developed for the imaging of microbe-induced HOCl production. Furthermore, we demonstrate dual oxidase (DUOX)-mediated HOCl generation in the mucosa of live animals providing a novel insight into mucosal innate immunity.</P> <P>Graphic Abstract</P><P>A specific and sensitive fluorescence-based method was developed for the imaging of microbe-induced HOCl production. <IMG SRC='http://pubs.rsc.org/services/images/RSCpubs.ePlatform.Service.FreeContent.ImageService.svc/ImageService/image/GA?id=c1cc10589b'> </P>
Lee, Yuree,Yoon, Taek Han,Lee, Jiyoun,Jeon, So Yeon,Lee, Jae Ho,Lee, Mi Kyoung,Chen, Huize,Yun, Ju,Oh, Se Yun,Wen, Xiaohong,Cho, Hui Kyung,Mang, Hyunggon,Kwak, June M. Elsevier 2018 Cell Vol.173 No.6
<P><B>Summary</B></P> <P>The cell wall, a defining feature of plants, provides a rigid structure critical for bonding cells together. To overcome this physical constraint, plants must process cell wall linkages during growth and development. However, little is known about the mechanism guiding cell-cell detachment and cell wall remodeling. Here, we identify two neighboring cell types in <I>Arabidopsis</I> that coordinate their activities to control cell wall processing, thereby ensuring precise abscission to discard organs. One cell type produces a honeycomb structure of lignin, which acts as a mechanical “brace” to localize cell wall breakdown and spatially limit abscising cells. The second cell type undergoes transdifferentiation into epidermal cells, forming protective cuticle, demonstrating <I>de novo</I> specification of epidermal cells, previously thought to be restricted to embryogenesis. Loss of the lignin brace leads to inadequate cuticle formation, resulting in surface barrier defects and susceptible to infection. Together, we show how plants precisely accomplish abscission.</P> <P><B>Highlights</B></P> <P> <UL> <LI> Two neighboring cell types coordinate cellular activities for organ separation </LI> <LI> A honeycomb structure of lignin acts as a “molecular brace” </LI> <LI> The lignin brace spatially restricts cell wall breakdown </LI> <LI> Lignin deposition ensures surface integrity of transdifferentiated epidermal cells </LI> </UL> </P> <P><B>Graphical Abstract</B></P> <P>[DISPLAY OMISSION]</P>
Bulk Switching Instrumentation Amplifier for a High-Impedance Source in Neural Signal Recording
Myungjin Han,Boram Kim,Yi-An Chen,Hyojung Lee,Seung-Han Park,Eunji Cheong,Jongill Hong,Gunhee Han,Youngcheol Chae IEEE 2015 IEEE Transactions on Circuits and Systems II: Expr Vol. No.
<P>Flicker noise is the most crucial issue in an instrumentation amplifier (IA) for neural recordings because low-frequency neural signals overlap with the frequency of the amplifier's flicker noise. A Chopping technique, often used to reduce the flicker noise, is not desirable for high-impedance input sources due to the charge injection and clock feedthrough from the MOSFETs of the input chopper to the signal source, resulting in a significant increase in the total input-referred noise. Whereas MOSFETs have less flicker noise at the moment of turning on, and the intrinsic flicker noise can be then reduced by turning on and off the MOSFETs in the IA. This brief proposes a bulk switching IA, which can avoid the input current noise. A prototype IA is implemented in a 65 nm CMOS occupying 0.053 mm<SUP>2</SUP>, and it achieves the input-referred noise of 0.74 μ<SUB>Vrms</SUB> (local field potential) for 100 k Ω source impedance, a 3.3 times reduction compared with that of the chopper IAs, while consuming only 3.96 μW from a 1.2 V supply.</P>
Jing-Han Chen,C.-T. Liang,D.H. Youn,Eun-Jin Lee,Gil-Ho Kim,Hun Park,Hyun-Ick Cho,Jung-Hee Lee,Jung-Kai Tsai,Jyun-Ying Lin,Y. F. Chen 한국물리학회 2006 THE JOURNAL OF THE KOREAN PHYSICAL SOCIETY Vol.48 No.6
AlGaN/GaN heterostructures have been attracting a great deal of interest because of their great potential applications as light-emitting-diodes, high-electron-mobility transistors (HEMTs), and detectors operating in the visible-to-ultraviolet range. The performances of these devices are governed by the electronic properties of the two-dimensional electron gas (2DEG) formed at the interface of AlGaN/GaN heterostructure. In this work, we report transport measurements for an AlGaN/GaN 2DEG as functions of the magnetic field B over a wide range of temperature (4.682 K T 80 K). At the highest measurement temperature of 80 K, the longitudinal resistance is nominally Bindependent, compelling experimental evidence for Drude-Boltzmann-like transport in a 2D system.
Ga-Eun Lee,Dohyun Jeung,Weidong Chen,Jiin Byun,Joo Young Lee,Han Chang Kang,Hye Suk Lee,Dae Joon Kim,Jin-Sung Choi,Cheol-Jung Lee,Hyun-Jung An,Yong-Yeon Cho 대한약학회 2023 Archives of Pharmacal Research Vol.46 No.1
E2F 1, 2, and 3a, (refer to as E2Fs) are a subfamily of E2F transcription factor family that play essential roles in cell-cycle progression, DNA replication, DNA repair, apoptosis, and differentiation. Although the transcriptional regulation of E2Fs has focused on pocket protein retinoblastoma protein complex, recent studies indicate that post-translational modification and stability regulation of E2Fs play key roles in diverse cellular processes. In this study, we found that FBXO1, a component of S-phase kinase-associated protein 1 (SKP1)-cullin 1-F-box protein (SCF) complex, is an E2Fs binding partner. Furthermore, FBXO1 to E2Fs binding induced K48 ubiquitination and subsequent proteasomal degradation of E2Fs. Binding domain analysis indicated that the Arg (R)/Ile (I) and R/Val (V) motifs, which are located in the dimerization domain of E2Fs, of E2F 1 and 3a and E2F2, respectively, acted as degron motifs (DMs) for FBXO1. Notably, RI/AA or RV/AA mutation in the DMs reduced FBXO1-mediated ubiquitination and prolonged the half-lives of E2Fs. Importantly, the stabilities of E2Fs were affected by phosphorylation of threonine residues located near RI and RV residues of DMs. Phosphorylation prediction database analysis and specific inhibitor analysis revealed that MEK/ERK signaling molecules play key roles in FBXO1/E2Fs’ interaction and modulate E2F protein turnover. Moreover, both elevated E2Fs protein levels by knockdown of FBXO1 and decreased E2Fs protein levels by sh-E2F3a delayed G1/S cell cycle transition, resulting in inhibition of cancer cell proliferation. These results demonstrated that FBXO1-E2Fs axis-mediated precise E2Fs stability regulation plays a key role in cell proliferation via G1/S cell cycle transition.
Pao-Huan Chen(Pao-Huan Chen),Chun-Ming Shih(Chun-Ming Shih),Chi-Kang Chang(Chi-Kang Chang),Chia-Pei Lin(Chia-Pei Lin),Yung-Han Chang(Yung-Han Chang),Hsin-Chien Lee(Hsin-Chien Lee),El-Wui Loh(El-Wui Lo 대한정신약물학회 2023 CLINICAL PSYCHOPHARMACOLOGY AND NEUROSCIENCE Vol.21 No.2
Objective: Predicting disease relapse and early intervention could reduce symptom severity. We attempted to identify potential indicators that predict the duration to next admission for an acute affective episode in patients with bipolar I disorder. Methods: We mathematically defined the duration to next psychiatric admission and performed single-variate regressions using historical data of 101 patients with bipolar I disorder to screen for potential variables for further multivariate regressions. Results: Age of onset, total psychiatric admissions, length of lithium use, and carbamazepine use during the psychiatric hospitalization contributed to the next psychiatric admission duration positively. The all-in-one found that hyperlipidemia during the psychiatric hospitalization demonstrated a negative contribution to the duration to next psychiatric admission; the last duration to psychiatric admission, lithium and carbamazepine uses during the psychiatric hospitalization, and heart rate on the discharge day positively contributed to the duration to next admission. Conclusion: We identified essential variables that may predict the duration of bipolar I patients’ next psychiatric admission. The correlation of a faster heartbeat and a normal lipid profile in delaying the next onset highlights the importance of managing these parameters when treating bipolar I disorder.
Chen, Cen,Li, Han,Kong, Xiangdong,Zhang, Sheng-Min,Lee, In-Seop Dove Medical Press 2015 INTERNATIONAL JOURNAL OF NANOMEDICINE Vol.10 No.-
<P>In this study, to improve the osseointegration of implants, osteogenic growth peptide (OGP) and fibronectin (FN) were loaded within mineral, which was formed on titanium, through adsorption and coprecipitation methods. The release profiles of OGP loaded by either adsorption or coprecipitation and the effects of the loading methods to immobilize OGP with and without FN on rat mesenchymal stem cell (rMSC) osteogenic differentiation were studied. The coprecipitation approach slightly reduced the initial burst release, while the adsorption approach provided a more sustained release. Dual loading of OGP and FN further improved cell attachments compared with either OGP or FN alone. Dually loaded OGP and FN also had a positive impact on rMSC proliferation and osteogenic differentiation. The difference in methods of loading OGP with and without FN also had some effects on osteogenic differentiation. Compared with coprecipitated OGP alone, adsorbed OGP enhanced later differentiation, such as osteocalcin secretion and matrix mineralization. Simultaneously adsorbed OGP and FN led to higher proliferation and higher osteogenic differentiation in both early and late stages compared with sequentially loaded OGP and FN. rMSC culture clearly indicated that simultaneously adsorbed OGP and FN could improve osseointegration, and this treatment represents a potential method for effective surface modification of dental and orthopedic implants.</P>