https://scholar.dgist.ac.kr/handle/20.500.11750/891 2026-04-04T13:09:28Z 2026-04-04T13:09:28Z Jeong, Jinju Kwon, Mi Kyung Nam, Yongho Lee, Chang-Hun Lee, Young-Sam https://scholar.dgist.ac.kr/handle/20.500.11750/57687 2025-07-25T02:42:52Z 2024-03-24T15:00:00Z

Title: The In vitro reconstituted the lens-specific intermediate filament with filensin and phakinin replicates the genotype-phenotype correlation for cataracts Author(s): Jeong, Jinju; Kwon, Mi Kyung; Nam, Yongho; Lee, Chang-Hun; Lee, Young-Sam Abstract: The intermediate filaments (IFs) family is one of the cyto-skeletons that regulate cell shape, size, stiffness, and movement. Unlike other cytoskeletons such as actin and tubulin, alpha-helical linear proteins of the IFs family constitute filament formation, which can be classified in six types depending on their assembly mechanisms. Filensin and phakinin, which are classified into the type-VI IFs, are only expressed in lens fiber cells and are composed of the lens-specific IFs. However, it is unclear how filensin and phakinin constitute filaments and have an impact on lens properties. Here, we studied the in vitro molecular assembly of human filensin and phakinin to identify the structural and functional relationships. We reconstituted the co-assembled filaments with human recombinant filensin and phakinin and determined its stoichiometry as the ratio of one-to-one. Filensin and phakinin filaments interacted with alpha-crystallin and assembled to make a beeded structure detected by the sedimentation assay and TEM. Moreover, the cataract disease mutant phakinin E233del caused short filaments and reduced resistance against heat and shear stress. We further showed that the alpha-helical rod domains in each protein are involved in the interaction between two proteins, and the intrinsically disordered head and tail domains regulates filament extension. Overall, we determined the molecular interaction in the lens-IFs, which confers the crystalline lens with stability against physical stress. These results suggest that the impaired integrity of the IF can lead to age-related diseases like cataracts and presbyopia.

2024-03-24T15:00:00Z Kang, Hyun Tae Park, Joon Tae Choi, Kobong Choi, Hyo Jei Jung, Chul Won Kim, Gyu Ree Lee, Young-Sam Park, Sang Chul https://scholar.dgist.ac.kr/handle/20.500.11750/47194 2025-07-25T04:08:42Z 2017-06-22T15:00:00Z

Title: Chemical screening identifies ROCK as a target for recoveringmitochondrial function in Hutchinson-Gilford progeria syndrome Author(s): Kang, Hyun Tae; Park, Joon Tae; Choi, Kobong; Choi, Hyo Jei; Jung, Chul Won; Kim, Gyu Ree; Lee, Young-Sam; Park, Sang Chul

2017-06-22T15:00:00Z 강현태 박준태 최고봉 김용섭 최효제 정철원 Lee, Young-Sam Park, Sang Chul https://scholar.dgist.ac.kr/handle/20.500.11750/47182 2025-07-25T04:25:21Z 2017-07-06T15:00:00Z

Title: Controlling Aging Restoration of Cellular Senescence Author(s): 강현태; 박준태; 최고봉; 김용섭; 최효제; 정철원; Lee, Young-Sam; Park, Sang Chul Abstract: Senescence is defined as an irreversible cell-cycle arrest and is the main driving-force of aging and age-related diseases. Recently, the reversal of senescence has been suggested as a promising target for rejuvenating organism or alleviating age-related pathologies. Cell physiology is regulated by complex signal pathways in which various kinase are involved. We hypothesized that aged altered cell physiology could be restored by modulating kinase activity, and performed high-throughput screening (HTS) with kinase inhibitor library to find compounds that can reverse senescence. From the chemical screening for agents that dismantle the cell cycle arrest of senescent cells and ameliorate aged-related phenotypic changes such as elevated SA-b-gal activity and reactive oxygen species concentration, Ataxia telangiectasia mutated (ATM) inhibitor as well as rho-associated, coiled-coil-containing protein kinase (ROCK) inhibitors were identified as effective agents. Since the role of ATM or ROCK in senescence remains elusive, the identification of novel interacting partners with these kinases would provide clues toward revealing its function in senescence and furthermore deciphering mode of action in reverting senescence by the kinase inhibitors. A yeast two-hybrid screen and further analysis confirmed that a subunit of vascular ATPase complex and a protein belonging to Rho family of GTPase are a novel substrate for ATM and ROCK, respectively. Attenuation of the aged-related kinase activation by the screened inhibitors reduced phosphorylation of the substrate protein, which induced functional recovery of lysosomes or mitochondria where the substrate is located. Our data revealed a novel mechanism in which reversal of senescence is controlled by the recovered lysosomal-mitochondrial axis upon adjustment of kinase activity.

2017-07-06T15:00:00Z 강현태 박준태 최고봉 김용섭 최효제 정철원 이영삼 박상철 https://scholar.dgist.ac.kr/handle/20.500.11750/47170 2025-07-25T02:40:09Z 2017-08-17T15:00:00Z

Title: Controlling Aging Restoration of Cellular Senescence Author(s): 강현태; 박준태; 최고봉; 김용섭; 최효제; 정철원; 이영삼; 박상철

2017-08-17T15:00:00Z