Browsing by Author "Liu, Zhaoqian"

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    The protective role of DOT1L in UV-induced melanomagenesis
    (Nature Publishing Group, 2018-01-17) Zhu, Bo; Chen, Shuyang; Wang, Hongshen; Yin, Chengqian; Han, Changpeng; Peng, Cong; Liu, Zhaoqian; Wan, Lixin; Zhang, Zhang; Zhang, Jie; Lian, Christine G.; Ma, Peilin; Xu, Zhi-xiang; Prince, Sharon; Wang, Tao; Gao, Xiumei; Shi, Yujiang; Liu, Dali; Liu, Min; Wei, Wenyi; Wei, Zhi; Pan, Jingxuan; Wang, Yongjun; Xuan, Zhenyu; Hess, Jay L.; Hayward, Nicholas K.; Goding, Colin R.; Chen, Xiang; Zhou, Jun; Cui, Rutao; Pathology and Laboratory Medicine, School of Medicine
    The DOT1L histone H3 lysine 79 (H3K79) methyltransferase plays an oncogenic role in MLL-rearranged leukemogenesis. Here, we demonstrate that, in contrast to MLL-rearranged leukemia, DOT1L plays a protective role in ultraviolet radiation (UVR)-induced melanoma development. Specifically, the DOT1L gene is located in a frequently deleted region and undergoes somatic mutation in human melanoma. Specific mutations functionally compromise DOT1L methyltransferase enzyme activity leading to reduced H3K79 methylation. Importantly, in the absence of DOT1L, UVR-induced DNA damage is inefficiently repaired, so that DOT1L loss promotes melanoma development in mice after exposure to UVR. Mechanistically, DOT1L facilitates DNA damage repair, with DOT1L-methylated H3K79 involvement in binding and recruiting XPC to the DNA damage site for nucleotide excision repair (NER). This study indicates that DOT1L plays a protective role in UVR-induced melanomagenesis.
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    Regulation of expression by promoters versus internal ribosome entry site in the 5′-untranslated sequence of the human cyclin-dependent kinase inhibitor p27
    (Oxford University Press, 2005-07-01) Liu, Zhaoqian; Dong, Zizheng; Han, Baoguang; Yang, Youyun; Liu, Yang; Zhang, Jian-Ting; Pharmacology and Toxicology, School of Medicine
    p27 kip1 regulates cell proliferation by binding to and inhibiting the activity of cyclin-dependent kinases and its expression oscillates with cell cycle. Recently, it has been suggested from studies using the traditional dicistronic DNA assay that the expression of p27 kip1 is regulated by internal ribosome entry site (IRES)-mediated translation initiation, and several RNA-binding protein factors were thought to play some role in this regulation. Considering the inevitable drawbacks of the dicistronic DNA assay, which could mislead a promoter activity or alternative splicing to IRES as previously demonstrated, we decided to reanalyze the 5′-untranslated region (5′-UTR) sequence of p27 kip1 and test whether it contains an IRES element or a promoter using more stringent methods, such as dicistronic RNA and promoterless dicistronic and monocistronic DNA assays. We found that the 5′-UTR sequence of human p27 kip1 does not have any significant IRES activity. The previously observed IRES activities are likely generated from the promoter activities present in the 5′-UTR sequences of p27 kip1 . The findings in this study indicate that transcriptional regulation likely plays an important role in p27 kip1 expression, and the mechanism of regulation of p27 expression by RNA-binding factors needs to be re-examined. The findings in this study also further enforce the importance that more stringent studies, such as promoterless dicistronic and monocistronic DNA and dicistronic RNA tests, are required to safeguard any future claims of cellular IRES.