Aberration of lipid storage in lipid droplets (LD) has been linked with the development and progression of several common metabolic diseases including obesity, type II diabetes,
Mono-ADP-ribosylation(MARylation)is a post-translational modification that regulates a variety of biological processes,including DNA damage repair,cell proliferation,metabolism,and stress and immune responses.In mamma...Mono-ADP-ribosylation(MARylation)is a post-translational modification that regulates a variety of biological processes,including DNA damage repair,cell proliferation,metabolism,and stress and immune responses.In mammals,MARylation is mainly catalyzed by ADP-ribosyltransferases(ARTs),which consist of two groups:ART cholera toxin-like(ARTCs)and ART diphtheria toxin-like(ARTDs,also known as PARPs).The human ARTC(hARTC)family is composed of four members:two active mono-ADP-ARTs(hARTC1 and hARTC5)and two enzymatically inactive enzymes(hARTC3 and hARTC4).In this study,we systematically examined the homology,expression,and localization pattern of the hARTC family,with a particular focus on hARTC1.Our results showed that hARTC3 interacted with hARTC1 and promoted the enzymatic activity of hARTC1 by stabilizing hARTC1.We also identified vesicle-associated membrane protein-associated protein B(VAPB)as a new target of hARTC1 and pinpointed Arg50 of VAPB as the ADP-ribosylation site.Furthermore,we demonstrated that knockdown of hARTC1 impaired intracellular calcium homeostasis,highlighting the functional importance of hARTC1-mediated VAPB Arg50 ADP-ribosylation in regulating calcium homeostasis.In summary,our study identified a new target of hARTC1 in the endoplasmic reticulum and suggested that ARTC1 plays a role in regulating calcium signaling.展开更多
文摘Aberration of lipid storage in lipid droplets (LD) has been linked with the development and progression of several common metabolic diseases including obesity, type II diabetes,
基金This work was supported by grants from the National Natural Science Foundation of China(32071277,82002594,81874160,and 32171295)the Natural Science Foundation of Hebei Province(C2021201012)+3 种基金S&T Program of Hebei(216Z2602G)the Interdisciplinary Research Program of Natural Science of Hebei University(DXK202006 and DXK202007)Hebei Natural Science Foundation for Outstanding Young Scholars(H2020201017)the High-level Talents Research Start-up Project of Hebei University(521000981352).
文摘Mono-ADP-ribosylation(MARylation)is a post-translational modification that regulates a variety of biological processes,including DNA damage repair,cell proliferation,metabolism,and stress and immune responses.In mammals,MARylation is mainly catalyzed by ADP-ribosyltransferases(ARTs),which consist of two groups:ART cholera toxin-like(ARTCs)and ART diphtheria toxin-like(ARTDs,also known as PARPs).The human ARTC(hARTC)family is composed of four members:two active mono-ADP-ARTs(hARTC1 and hARTC5)and two enzymatically inactive enzymes(hARTC3 and hARTC4).In this study,we systematically examined the homology,expression,and localization pattern of the hARTC family,with a particular focus on hARTC1.Our results showed that hARTC3 interacted with hARTC1 and promoted the enzymatic activity of hARTC1 by stabilizing hARTC1.We also identified vesicle-associated membrane protein-associated protein B(VAPB)as a new target of hARTC1 and pinpointed Arg50 of VAPB as the ADP-ribosylation site.Furthermore,we demonstrated that knockdown of hARTC1 impaired intracellular calcium homeostasis,highlighting the functional importance of hARTC1-mediated VAPB Arg50 ADP-ribosylation in regulating calcium homeostasis.In summary,our study identified a new target of hARTC1 in the endoplasmic reticulum and suggested that ARTC1 plays a role in regulating calcium signaling.
