The Experts below are selected from a list of 19215 Experts worldwide ranked by ideXlab platform
Zhongjun Zhou - One of the best experts on this subject based on the ideXlab platform.
-
LAmin A is An endogenous sirt6 ActivAtor And promotes sirt6 mediAted dnA repAir
Cell Reports, 2015Co-Authors: Shrestha Ghosh, Yi Wang, Zhongjun ZhouAbstract:The nucleAr LAmins Are essentiAl for vArious moleculAr events in the nucleus, such As chromAtin orgAnizAtion, DNA replicAtion, And provision of mechAnicAl support. A specific point mutAtion in the LMNA gene creAtes A truncAted preLAmin A termed progerin, cAusing Hutchinson-Gilford progeriA syndrome (HGPS). SIRT6 deficiency leAds to defective genomic mAintenAnce And AccelerAted Aging similAr to HGPS, suggesting A potentiAl link between LAmin A And SIRT6. Here, we report thAt LAmin A is An endogenous ActivAtor of SIRT6 And fAcilitAtes chromAtin locAlizAtion of SIRT6 upon DNA dAmAge. LAmin A promotes SIRT6-dependent DNA-PKcs (DNA-PK cAtAlytic subunit) recruitment to chromAtin, CtIP deAcetylAtion, And PARP1 mono-ADP ribosylAtion in response to DNA dAmAge. The presence of progerin jeopArdizes SIRT6 ActivAtion And compromises SIRT6-mediAted moleculAr events in response to DNA dAmAge. These dAtA reveAl A criticAl role for LAmin A in regulAting SIRT6 Activities, suggesting thAt defects in SIRT6 functions contribute to impAired DNA repAir And AccelerAted Aging in HGPS.
-
LAmin A/C, LAminopAthies And premAture Ageing.
Histology and histopathology, 2008Co-Authors: Baohua Liu, Zhongjun ZhouAbstract:LAmin A/C belongs to type V intermediAte filAments And constitutes the nucleAr LAminA And nucleAr mAtrix, where A vAriety of nucleAr Activities occur. LAmin A/C protein is firstly synthesized As A precursor And is further proteolyticAlly processed by the zinc metAllo-proteinAse Ste24 (Zmpste24). LAmin A/C mutAtions cAuse A series of humAn diseAses, collectively cAlled LAminopAthies, the most severe of which is Hutchinson Gilford progeriA syndrome (HGPS) And restrictive dermopAthy (RD) which Arises due to An unsuccessful mAturAtion of preLAmin A. Although the exAct underlying moleculAr mechAnisms Are still poorly understood, genomic instAbility, defective nucleAr mechAnics And mechAnotrAnsduction, hAve been hypothesized to be responsible for LAminopAthy-bAsed premAture Ageing. RemovAl of unprocessed preLAmin A (progerin) or rescue of defective DNA repAir could be potentiAl therApeutic strAtegies for the treAtment of HGPS in future.
-
Review LAmin A/C, LAminopAthies And premAture Ageing
2008Co-Authors: Baohua Liu, Zhongjun ZhouAbstract:SummAry. LAmin A/C belongs to type V intermediAte filAments And constitutes the nucleAr LAminA And nucleAr mAtrix, where A vAriety of nucleAr Activities occur. LAmin A/C protein is firstly synthesized As A precursor And is further proteolyticAlly processed by the zinc metAllo-proteinAse Ste24 (Zmpste24). LAmin A/C mutAtions cAuse A series of humAn diseAses, collectively cAlled LAminopAthies, the most severe of which is Hutchinson Gilford progeriA syndrome (HGPS) And restrictive dermopAthy (RD) which Arises due to An unsuccessful mAturAtion of preLAmin A. Although the exAct underlying moleculAr mechAnisms Are still poorly understood, genomic instAbility, defective nucleAr mechAnics And mechAnotrAnsduction, hAve been hypothesized to be responsible for LAminopAthy-bAsed premAture Ageing. RemovAl of unprocessed preLAmin A (progerin) or rescue of defective DNA repAir could be potentiAl therApeutic strAtegies for the treAtment of HGPS in future.
Kyujin Chung - One of the best experts on this subject based on the ideXlab platform.
-
interruption of progerin LAmin A c binding AmeliorAtes hutchinson gilford progeriA syndrome phenotype
Journal of Clinical Investigation, 2016Co-Authors: Su Jin Lee, Youn Sang Jung, Min Ho Yoon, So Mi Kang, Jee Hyun Lee, So Young Jun, Tae Gyun Woo, Ho Young Chun, Sang Kyum Kim, Kyujin ChungAbstract:Hutchinson-Gilford progeriA syndrome (HGPS) is A rAre AutosomAl dominAnt genetic diseAse thAt is cAused by A silent mutAtion of the LMNA gene encoding LAmins A And C (LAmin A/C). The G608G mutAtion generAtes A more Accessible splicing donor site thAn does WT And produces An AlternAtively spliced product of LMNA cAlled progerin, which is Also expressed in normAl Aged cells. In this study, we determined thAt progerin binds directly to LAmin A/C And induces profound nucleAr AberrAtions. Given this observAtion, we performed A rAndom screening of A chemicAl librAry And identified 3 compounds (JH1, JH4, And JH13) thAt efficiently block progerin-LAmin A/C binding. These 3 chemicAls, pArticulArly JH4, AlleviAted nucleAr deformAtion And reversed senescence mArkers chArActeristic of HGPS cells, including growth Arrest And senescence-AssociAted β-gAl (SA-β-gAl) Activity. We then used microArrAy-bAsed AnAlysis to demonstrAte thAt JH4 is Able to rescue defects of cell-cycle progression in both HGPS And Aged cells. Furthermore, AdministrAtion of JH4 to LmnAG609G/G609G-mutAnt mice, which phenocopy humAn HGPS, resulted in A mArked improvement of severAl progeriA phenotypes And An extended lifespAn. Together, these findings indicAte thAt specific inhibitors with the Ability to block pAthologicAl progerin-LAmin A/C binding mAy represent A promising strAtegy for improving lifespAn And heAlth in both HGPS And normAl Aging.
Shrestha Ghosh - One of the best experts on this subject based on the ideXlab platform.
-
results i LAmin A is An endogenous ActivAtor of sirt6 in dnA dAmAge repAir process
2019Co-Authors: Shrestha GhoshAbstract:This chApter illustrAtes the functionAl interAction between SIRT6 And LAmin A, estAblishing LAmin A to be A positive regulAtor of SIRT6 in DNA dAmAge responses. It Also sheds light on the impAired ActivAtion of SIRT6 by A mutAnt form of LAmin A (Progerin), which remAins upregulAted in Hutchinson-Gilford ProgeriA Syndrome (HGPS), thus implicAting impAired functioning of SIRT6 As A cAusAtive fActor in HGPS (Ghosh et Al. in Cell Rep 13:1396–1406, [1]).
-
LAmin A is An endogenous sirt6 ActivAtor And promotes sirt6 mediAted dnA repAir
Cell Reports, 2015Co-Authors: Shrestha Ghosh, Yi Wang, Zhongjun ZhouAbstract:The nucleAr LAmins Are essentiAl for vArious moleculAr events in the nucleus, such As chromAtin orgAnizAtion, DNA replicAtion, And provision of mechAnicAl support. A specific point mutAtion in the LMNA gene creAtes A truncAted preLAmin A termed progerin, cAusing Hutchinson-Gilford progeriA syndrome (HGPS). SIRT6 deficiency leAds to defective genomic mAintenAnce And AccelerAted Aging similAr to HGPS, suggesting A potentiAl link between LAmin A And SIRT6. Here, we report thAt LAmin A is An endogenous ActivAtor of SIRT6 And fAcilitAtes chromAtin locAlizAtion of SIRT6 upon DNA dAmAge. LAmin A promotes SIRT6-dependent DNA-PKcs (DNA-PK cAtAlytic subunit) recruitment to chromAtin, CtIP deAcetylAtion, And PARP1 mono-ADP ribosylAtion in response to DNA dAmAge. The presence of progerin jeopArdizes SIRT6 ActivAtion And compromises SIRT6-mediAted moleculAr events in response to DNA dAmAge. These dAtA reveAl A criticAl role for LAmin A in regulAting SIRT6 Activities, suggesting thAt defects in SIRT6 functions contribute to impAired DNA repAir And AccelerAted Aging in HGPS.
Su Jin Lee - One of the best experts on this subject based on the ideXlab platform.
-
interruption of progerin LAmin A c binding AmeliorAtes hutchinson gilford progeriA syndrome phenotype
Journal of Clinical Investigation, 2016Co-Authors: Su Jin Lee, Youn Sang Jung, Min Ho Yoon, So Mi Kang, Jee Hyun Lee, So Young Jun, Tae Gyun Woo, Ho Young Chun, Sang Kyum Kim, Kyujin ChungAbstract:Hutchinson-Gilford progeriA syndrome (HGPS) is A rAre AutosomAl dominAnt genetic diseAse thAt is cAused by A silent mutAtion of the LMNA gene encoding LAmins A And C (LAmin A/C). The G608G mutAtion generAtes A more Accessible splicing donor site thAn does WT And produces An AlternAtively spliced product of LMNA cAlled progerin, which is Also expressed in normAl Aged cells. In this study, we determined thAt progerin binds directly to LAmin A/C And induces profound nucleAr AberrAtions. Given this observAtion, we performed A rAndom screening of A chemicAl librAry And identified 3 compounds (JH1, JH4, And JH13) thAt efficiently block progerin-LAmin A/C binding. These 3 chemicAls, pArticulArly JH4, AlleviAted nucleAr deformAtion And reversed senescence mArkers chArActeristic of HGPS cells, including growth Arrest And senescence-AssociAted β-gAl (SA-β-gAl) Activity. We then used microArrAy-bAsed AnAlysis to demonstrAte thAt JH4 is Able to rescue defects of cell-cycle progression in both HGPS And Aged cells. Furthermore, AdministrAtion of JH4 to LmnAG609G/G609G-mutAnt mice, which phenocopy humAn HGPS, resulted in A mArked improvement of severAl progeriA phenotypes And An extended lifespAn. Together, these findings indicAte thAt specific inhibitors with the Ability to block pAthologicAl progerin-LAmin A/C binding mAy represent A promising strAtegy for improving lifespAn And heAlth in both HGPS And normAl Aging.
-
Interruption of progerin–LAmin A/C binding AmeliorAtes Hutchinson-Gilford progeriA syndrome phenotype
Journal of Clinical Investigation, 2016Co-Authors: Su Jin Lee, Youn Sang Jung, Min Ho Yoon, So Mi Kang, Jee Hyun Lee, So Young Jun, Tae Gyun Woo, Ho Young Chun, Sang Kyum KimAbstract:Hutchinson-Gilford progeriA syndrome (HGPS) is A rAre AutosomAl dominAnt genetic diseAse thAt is cAused by A silent mutAtion of the LMNA gene encoding LAmins A And C (LAmin A/C). The G608G mutAtion generAtes A more Accessible splicing donor site thAn does WT And produces An AlternAtively spliced product of LMNA cAlled progerin, which is Also expressed in normAl Aged cells. In this study, we determined thAt progerin binds directly to LAmin A/C And induces profound nucleAr AberrAtions. Given this observAtion, we performed A rAndom screening of A chemicAl librAry And identified 3 compounds (JH1, JH4, And JH13) thAt efficiently block progerin-LAmin A/C binding. These 3 chemicAls, pArticulArly JH4, AlleviAted nucleAr deformAtion And reversed senescence mArkers chArActeristic of HGPS cells, including growth Arrest And senescence-AssociAted β-gAl (SA-β-gAl) Activity. We then used microArrAy-bAsed AnAlysis to demonstrAte thAt JH4 is Able to rescue defects of cell-cycle progression in both HGPS And Aged cells. Furthermore, AdministrAtion of JH4 to LmnAG609G/G609G-mutAnt mice, which phenocopy humAn HGPS, resulted in A mArked improvement of severAl progeriA phenotypes And An extended lifespAn. Together, these findings indicAte thAt specific inhibitors with the Ability to block pAthologicAl progerin-LAmin A/C binding mAy represent A promising strAtegy for improving lifespAn And heAlth in both HGPS And normAl Aging.
Kevin D. Sarge - One of the best experts on this subject based on the ideXlab platform.
-
sumoylAtion regulAtes LAmin A function And is lost in LAmin A mutAnts AssociAted with fAmiliAl cArdiomyopAthies
Journal of Cell Biology, 2008Co-Authors: Yuqian Zhang, Kevin D. SargeAbstract:LAmin A mutAtions cAuse mAny diseAses, including cArdiomyopAthies And ProgeriA Syndrome. The covAlent AttAchment of smAll ubiquitin-like modifier (SUMO) polypeptides regulAtes the function of mAny proteins. Until now, no exAmples of humAn diseAse-cAusing mutAtions thAt occur within A sumoylAtion consensus sequence And Alter sumoylAtion were known. We show thAt LAmin A is sumoylAted At lysine 201 And thAt two LAmin A mutAnts AssociAted with fAmiliAl dilAted cArdiomyopAthy, E203G And E203K, exhibit decreAsed sumoylAtion. E203 occupies the conserved +2 position in the sumoylAtion consensus ΨKXE. LAmin A mutAnts E203G, E203K, And K201R All exhibit A similAr AberrAnt subcellulAr locAlizAtion And Are AssociAted with increAsed cell deAth. FibroblAsts from An individuAl with the E203K LAmin A mutAtion Also exhibit decreAsed LAmin A sumoylAtion And increAsed cell deAth. These results suggest thAt SUMO modificAtion is importAnt for normAl LAmin A function And implicAte An involvement for Altered sumoylAtion in the E203G/E203K LAmin A cArdiomyopAthies.
