Polyprenylated acylphloroglucinols represent an important class of natural products found in many plants.Among them,the two related products oblongifolin C(Ob-C)and guttiferone K(Gt-K)isolated from Garcinia species(no...Polyprenylated acylphloroglucinols represent an important class of natural products found in many plants.Among them,the two related products oblongifolin C(Ob-C)and guttiferone K(Gt-K)isolated from Garcinia species(notably from edible fruits),have attracted attention due to their marked anticancer properties.The two compounds only differ by the nature of the C-6 side chain,prenyl(Gt-K)or geranyl(Ob-C)on the phloroglucinol core.Their origin,method of extraction and biological properties are presented here,with a focus on the targets and pathways implicated in their anticancer activities.Both compounds markedly reduce cancer cell proliferation in vitro,as well as tumor growth and metastasis in vivo.They are both potent inducer of tumor cell apoptosis,and regulation of autophagy flux is a hallmark of their mode of action.The distinct mechanism leading to autophagosome accumulation in cells and the implicated molecular targets are discussed.The specific role of the chaperone protein HSPA8,known to interact with Ob-C,is addressed.Molecular models of Gt-K and Ob-C bound to HSPA8 provide a structural basis to their common HSPA8-binding recognition capacity.The review shed light on the mechanism of action of these compounds,to encourage their studies and potential development.展开更多
The tumor suppressr p73 is a homolog of p53 and is capable of inducing cell cycle arrest and apoptosis.Here,we identify nerve growth factor receptor(NGFR,p75NTR,or CD271)as a novel negative p73 regulator.p73 activates...The tumor suppressr p73 is a homolog of p53 and is capable of inducing cell cycle arrest and apoptosis.Here,we identify nerve growth factor receptor(NGFR,p75NTR,or CD271)as a novel negative p73 regulator.p73 activates NGFR transcription,which,in turn,promotes p73 degradation in a negative feedback loop.NGFR directly binds to p73 central DNA-binding domain and suppresses p73 transcriptional activity as well as p73-mediated apoptosis in cancer cells.Surprisingly,we uncover a previously unknown mechanism of NGFR-facilitated p73 degradation through the chaperone-mediated autophagy(CMA)pathway.Collectively,our studies demonstrate a new oncogenic function for NGFR in inactivating p73 activity by promoting its degradation through the CMA.展开更多
文摘Polyprenylated acylphloroglucinols represent an important class of natural products found in many plants.Among them,the two related products oblongifolin C(Ob-C)and guttiferone K(Gt-K)isolated from Garcinia species(notably from edible fruits),have attracted attention due to their marked anticancer properties.The two compounds only differ by the nature of the C-6 side chain,prenyl(Gt-K)or geranyl(Ob-C)on the phloroglucinol core.Their origin,method of extraction and biological properties are presented here,with a focus on the targets and pathways implicated in their anticancer activities.Both compounds markedly reduce cancer cell proliferation in vitro,as well as tumor growth and metastasis in vivo.They are both potent inducer of tumor cell apoptosis,and regulation of autophagy flux is a hallmark of their mode of action.The distinct mechanism leading to autophagosome accumulation in cells and the implicated molecular targets are discussed.The specific role of the chaperone protein HSPA8,known to interact with Ob-C,is addressed.Molecular models of Gt-K and Ob-C bound to HSPA8 provide a structural basis to their common HSPA8-binding recognition capacity.The review shed light on the mechanism of action of these compounds,to encourage their studies and potential development.
基金H.L. and S.X.Z.were supported in part by NIH-NCI grants(R01CA095441,R01CA17246 and R01CA127724).
文摘The tumor suppressr p73 is a homolog of p53 and is capable of inducing cell cycle arrest and apoptosis.Here,we identify nerve growth factor receptor(NGFR,p75NTR,or CD271)as a novel negative p73 regulator.p73 activates NGFR transcription,which,in turn,promotes p73 degradation in a negative feedback loop.NGFR directly binds to p73 central DNA-binding domain and suppresses p73 transcriptional activity as well as p73-mediated apoptosis in cancer cells.Surprisingly,we uncover a previously unknown mechanism of NGFR-facilitated p73 degradation through the chaperone-mediated autophagy(CMA)pathway.Collectively,our studies demonstrate a new oncogenic function for NGFR in inactivating p73 activity by promoting its degradation through the CMA.
