title: Interaction of Heat Shock Protein Cpn10 with the Cyclin E/Cdk2 Substrate Nuclear Protein Ataxia-Telangiectasia (NPAT) Is Involved in Regulating Histone Transcription.
abstract: Precise modulation of histone gene transcription is critical for cell cycle progression. As a direct substrate of Cyclin E/CDK2, nuclear protein ataxia-telangiectasia (NPAT) is a crucial factor in regulating histone transcription and cell cycle progression. Here we identified that Cpn10/HSPE, a 10-kDa heat shock protein, is a novel interacting partner of NPAT. A pool of Cpn10 is colocalized with NPAT foci during G1 and S phases in nuclei. Gain- and loss-of-function experiments unraveled an essential role of Cpn10 in histone transcription. A conserved DLFD motif within Cpn10 was critical for targeting NPAT and modulating histone transcription. More importantly, knockdown of Cpn10 disrupted the focus formation of both NPAT and FADD-like interleukin-1β-converting enzyme-associated huge protein without affecting Coilin-positive Cajal bodies. Finally, Cpn10 is important for S phase progression and cell proliferation. Taken together, our finding revealed a novel role of Cpn10 in the spatial regulation of NPAT signaling and disclosed a previously unappreciated link between the heat shock protein and histone transcription regulation.
authors.affiliation: From the Department of Biochemistry and Molecular Biology.
authors.forename: Li
authors.initials: L
authors.lastname: Ling Zheng
authors.affiliation: From the Department of Biochemistry and Molecular Biology.
authors.forename: Fei Ya
authors.initials: FY
authors.lastname: Wang
authors.affiliation: From the Department of Biochemistry and Molecular Biology, Key Laboratory of Tissue Engineering and Regenerative Medicine of Zhejiang Province, Center for Stem Cell and Regenerative Medicine, and.
authors.forename: Xiao Xia
authors.initials: XX
authors.lastname: Cong
authors.affiliation: Department of Orthopaedic Surgery, Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang 310058, China.
authors.forename: Yue
authors.initials: Y
authors.lastname: Shen
authors.affiliation: From the Department of Biochemistry and Molecular Biology, Key Laboratory of Tissue Engineering and Regenerative Medicine of Zhejiang Province, Center for Stem Cell and Regenerative Medicine, and.
authors.forename: Xi Sheng
authors.initials: XS
authors.lastname: Rao
authors.affiliation: From the Department of Biochemistry and Molecular Biology, Key Laboratory of Tissue Engineering and Regenerative Medicine of Zhejiang Province, Center for Stem Cell and Regenerative Medicine, and.
authors.forename: Dao Sheng
authors.initials: DS
authors.lastname: Huang
authors.affiliation: From the Department of Biochemistry and Molecular Biology, Key Laboratory of Tissue Engineering and Regenerative Medicine of Zhejiang Province, Center for Stem Cell and Regenerative Medicine, and.
authors.forename: Wei
authors.initials: W
authors.lastname: Fan
authors.affiliation: From the Department of Biochemistry and Molecular Biology, Key Laboratory of Tissue Engineering and Regenerative Medicine of Zhejiang Province, Center for Stem Cell and Regenerative Medicine, and.
authors.forename: Peng
authors.initials: P
authors.lastname: Yi
authors.affiliation: the Department of Abdominal Tumor Surgery, Zhejiang Cancer Hospital, Hangzhou, Zhejiang 310022, China, and.
authors.forename: Xin Bao
authors.initials: XB
authors.lastname: Wang
authors.affiliation: the Department of Surgery and Sidney Kimmel Cancer Center, Johns Hopkins University School of Medicine, Baltimore, Maryland 21231.
authors.forename: Lei
authors.initials: L
authors.lastname: Zheng
authors.affiliation: From the Department of Biochemistry and Molecular Biology, Key Laboratory of Tissue Engineering and Regenerative Medicine of Zhejiang Province, Center for Stem Cell and Regenerative Medicine, and zhouyt@zju.edu.cn.
authors.forename: Yi Ting
authors.initials: YT
authors.lastname: Zhou
authors.affiliation: From the Department of Biochemistry and Molecular Biology, luoyan2011@zju.edu.cn.
authors.forename: Yan
authors.initials: Y
authors.lastname: Luo
mesh_terms: D020816:Amino Acid Motifs; D002453:Cell Cycle; D018797:Cell Cycle Proteins / Q000378:metabolism*; D002467:Cell Nucleus / Q000378:metabolism; D049109:Cell Proliferation; D018835:Chaperonin 10 / Q000378:metabolism*; D019927:Cyclin E / Q000378:metabolism*; D051357:Cyclin-Dependent Kinase 2 / Q000378:metabolism*; D018450:Disease Progression; D006367:HeLa Cells; D006657:Histones / Q000378:metabolism*; D006801:Humans; D008856:Microscopy, Fluorescence; D009687:Nuclear Proteins / Q000378:metabolism*; D011257:Pregnancy Proteins / Q000378:metabolism*; D034622:RNA Interference; D015398:Signal Transduction; D013491:Suppressor Factors, Immunologic / Q000378:metabolism*; D014158:Transcription, Genetic; D020798:Two-Hybrid System Techniques
chemical_list: D018797:Cell Cycle Proteins; D018835:Chaperonin 10; D019927:Cyclin E; D006657:Histones; C101693:NPAT protein, human; D009687:Nuclear Proteins; D011257:Pregnancy Proteins; D013491:Suppressor Factors, Immunologic; C025124:early pregnancy factor; C495894:CDK2 protein, human; D051357:Cyclin-Dependent Kinase 2
keywords: Cpn10; NPAT; cell cycle; cell proliferation; cyclin; heat shock protein (HSP); histone; histone transcription