The pigmentation in the liver of Chinese fire-bellied newt(Cynops orientalis) was described during two periods of the annual cycle(summer activity and winter hibernation). A large number of melanin granules were gathe...The pigmentation in the liver of Chinese fire-bellied newt(Cynops orientalis) was described during two periods of the annual cycle(summer activity and winter hibernation). A large number of melanin granules were gathered into clusters and distributed unevenly inside the pigment cells. Liver pigmentation(melanin content) was found unstable,varying during the annual cycle. During the hibernation period,pigmentation accumulation was shown to increase in the liver of the Chinese fire-bellied newt. Hepatocytes during the active period are approximately 14.64% larger than those in the hibernation period,while the nucleus is approximately 7.43% bigger during the active period when compared with that during the hibernation period. These findings indicate that variation in pigment distribution and hepatocyte morphology in Chinese fire-bellied newt liver may be an ecologically adaptive strategy to the adverse physiological conditions during hibernation.展开更多
Doublecortin-like kinase 1(DCLK1)is upregulated in many tumors and is a marker for tumor stem cells.Accumulating evidence suggests DCLK1 constitutes a promising drug target for cancer therapy.However,the regulation of...Doublecortin-like kinase 1(DCLK1)is upregulated in many tumors and is a marker for tumor stem cells.Accumulating evidence suggests DCLK1 constitutes a promising drug target for cancer therapy.However,the regulation of DCLK1 kinase activity is poorly understood,particularly the function of its autoinhibitory domain(AID),and,moreover,no physiological activators of DCLK1 have presently been reported.Here we determined the first DCLK1 kinase structure in the autoinhibited state and identified the neuronal calcium sensor HPCAL1 as an activator of DCLK1.The C-terminal AID functions to block the ATP-binding site and is competitive with ATP.HPCAL1 binds directly to the AID in a Ca^(2+)-dependent manner,which releases the autoinhibition.We also analyzed cancer-associated mutations occurring in the AID and elucidate how these mutations disrupt DCLK1 autoinhibition to elicit kinase activity upregulation.Our results present a molecular mechanism for autoinhibition and activation of DCLK1 kinase activity and provide insights into DCLK1-associated tumorigenesis.展开更多
基金supported by the initial funding from Henan University of Urban Construction and a grant from the Foundational and Advanced Techniques Foundation of Henan, China (122300410356).
文摘The pigmentation in the liver of Chinese fire-bellied newt(Cynops orientalis) was described during two periods of the annual cycle(summer activity and winter hibernation). A large number of melanin granules were gathered into clusters and distributed unevenly inside the pigment cells. Liver pigmentation(melanin content) was found unstable,varying during the annual cycle. During the hibernation period,pigmentation accumulation was shown to increase in the liver of the Chinese fire-bellied newt. Hepatocytes during the active period are approximately 14.64% larger than those in the hibernation period,while the nucleus is approximately 7.43% bigger during the active period when compared with that during the hibernation period. These findings indicate that variation in pigment distribution and hepatocyte morphology in Chinese fire-bellied newt liver may be an ecologically adaptive strategy to the adverse physiological conditions during hibernation.
基金Financial support for this work was provided by the National Natural Science Foundation of China(31741027,82103226,81672722,and 81501368)Natural Science Foundation of Henan Province(212300410243).
文摘Doublecortin-like kinase 1(DCLK1)is upregulated in many tumors and is a marker for tumor stem cells.Accumulating evidence suggests DCLK1 constitutes a promising drug target for cancer therapy.However,the regulation of DCLK1 kinase activity is poorly understood,particularly the function of its autoinhibitory domain(AID),and,moreover,no physiological activators of DCLK1 have presently been reported.Here we determined the first DCLK1 kinase structure in the autoinhibited state and identified the neuronal calcium sensor HPCAL1 as an activator of DCLK1.The C-terminal AID functions to block the ATP-binding site and is competitive with ATP.HPCAL1 binds directly to the AID in a Ca^(2+)-dependent manner,which releases the autoinhibition.We also analyzed cancer-associated mutations occurring in the AID and elucidate how these mutations disrupt DCLK1 autoinhibition to elicit kinase activity upregulation.Our results present a molecular mechanism for autoinhibition and activation of DCLK1 kinase activity and provide insights into DCLK1-associated tumorigenesis.
