title: Nucleophosmin Interacts with PIN2/TERF1-interacting Telomerase Inhibitor 1 (PinX1) and Attenuates the PinX1 Inhibition on Telomerase Activity.
abstract: Telomerase activation and telomere maintenance are critical for cellular immortalization and transformation. PIN2/TERF1-interacting telomerase inhibitor 1 (PinX1) is a telomerase regulator and the aberrant expression of PinX1 causes telomere shortening. Identifying PinX1-interacting proteins is important for understanding telomere maintenance. We found that PinX1 directly interacts with nucleophosmin (NPM), a protein that has been shown to positively correlate with telomerase activity. We further showed that PinX1 acts as a linker in the association between NPM and hTERT, the catalytic subunit of telomerase. Additionally, the recruitment of NPM by PinX1 to the telomerase complex could partially attenuate the PinX1-mediated inhibition on telomerase activity. Taken together, our data reveal a novel mechanism that regulates telomerase activation through the interaction between NPM, PinX1 and the telomerase complex.
authors.affiliation: Centre for Protein Science and Crystallography, School of Life Sciences, The Chinese University of Hong Kong, Shatin, N.T., Hong Kong, China.
authors.forename: Derek Hang-Cheong
authors.initials: DH
authors.lastname: Cheung
authors.affiliation: Centre for Protein Science and Crystallography, School of Life Sciences, The Chinese University of Hong Kong, Shatin, N.T., Hong Kong, China.
authors.forename: Sai-Tim
authors.initials: ST
authors.lastname: Ho
authors.affiliation: Centre for Protein Science and Crystallography, School of Life Sciences, The Chinese University of Hong Kong, Shatin, N.T., Hong Kong, China.
authors.forename: Kwok-Fai
authors.initials: KF
authors.lastname: Lau
authors.affiliation: Laboratory of Tumor and Molecular Biology, Beijing Institute of Biotechnology, Beijing, China.
authors.forename: Rui
authors.initials: R
authors.lastname: Jin
authors.affiliation: Laboratory of Tumor and Molecular Biology, Beijing Institute of Biotechnology, Beijing, China.
authors.forename: Ya-Nan
authors.initials: YN
authors.lastname: Wang
authors.affiliation: Stanley Ho Center for Emerging Infectious Diseases, Li Ka-Shing Medical Institute, The Chinese University of Hong Kong, Shatin, N.T., Hong Kong, China.
authors.forename: Hsiang-Fu
authors.initials: HF
authors.lastname: Kung
authors.affiliation: Laboratory of Tumor and Molecular Biology, Beijing Institute of Biotechnology, Beijing, China.
authors.forename: Jun-Jian
authors.initials: JJ
authors.lastname: Huang
authors.affiliation: Centre for Protein Science and Crystallography, School of Life Sciences, The Chinese University of Hong Kong, Shatin, N.T., Hong Kong, China.
authors.forename: Pang-Chui
authors.initials: PC
authors.lastname: Shaw
mesh_terms: D018797:Cell Cycle Proteins; D002460:Cell Line; D004789:Enzyme Activation; D006801:Humans; D046912:Multiprotein Complexes; D009687:Nuclear Proteins / Q000737:chemistry / Q000378:metabolism*; D000090243:Nucleophosmin; D011485:Protein Binding; D011487:Protein Conformation; D054730:Protein Interaction Domains and Motifs; D019098:Telomerase / Q000037:antagonists & inhibitors / Q000737:chemistry / Q000378:metabolism*; D025521:Tumor Suppressor Proteins / Q000737:chemistry / Q000378:metabolism*
chemical_list: D018797:Cell Cycle Proteins; D046912:Multiprotein Complexes; C000716967:NPM1 protein, human; D009687:Nuclear Proteins; C440808:PINX1 protein, human; D025521:Tumor Suppressor Proteins; D000090243:Nucleophosmin; D019098:Telomerase