PinX1 is a novel microtubule-binding protein essential for accurate chromosome segregation.
Mitosis is an orchestration of dynamic interactions between spindle microtubules and chromosomes, which is mediated by protein structures that include the kinetochores, and other protein complexes present on chromosomes. PinX1 is a potent telomerase inhibitor in interphase; however, its function in mitosis is not well documented. Here we show that PinX1 is essential for faithful chromosome segregation. Deconvolution microscopic analyses show that PinX1 localizes to nucleoli and telomeres in interphase and relocates to the periphery of chromosomes and the outer plate of the kinetochores in mitosis. Our deletion analyses mapped the kinetochore localization domain of PinX1 to the central region and its chromosome periphery localization domain to the C terminus. Interestingly, the kinetochore localization of PinX1 is dependent on Hec1 and CENP-E. Our biochemical characterization revealed that PinX1 is a novel microtubule-binding protein. Our real time imaging analyses show that suppression of PinX1 by small interference RNA abrogates faithful chromosome segregation and results in anaphase chromatid bridges in mitosis and micronuclei in interphase, suggesting an essential role of PinX1 in chromosome stability. Taken together, the results indicate that PinX1 plays an important role in faithful chromosome segregation in mitosis.
Yuan
Kai
K
Anhui Key Laboratory for Cellular Dynamics and Chemical Biology and Hefei National Laboratory for Physical Sciences at the Nanoscale, Hefei 230027, China.
Li
Na
N
Jiang
Kai
K
Zhu
Tongge
T
Huo
Yuda
Y
Wang
Chong
C
Lu
Jing
J
Shaw
Andrew
A
Thomas
Kelwyn
K
Zhang
Jiancun
J
Mann
David
D
Liao
Jian
J
Jin
Changjiang
C
Yao
Xuebiao
X
D018797:Cell Cycle Proteins; D002868:Chromosomal Proteins, Non-Histone / Q000235:genetics / Q000502:physiology; D020090:Chromosome Segregation / Q000235:genetics / Q000502:physiology*; D003598:Cytoskeletal Proteins; D006367:HeLa Cells; D006801:Humans; D018386:Kinetochores / Q000378:metabolism; D008856:Microscopy, Fluorescence; D008870:Microtubules / Q000378:metabolism*; D008938:Mitosis / Q000235:genetics / Q000502:physiology; D009687:Nuclear Proteins / Q000235:genetics / Q000502:physiology; D011485:Protein Binding / Q000235:genetics / Q000502:physiology; D034741:RNA, Small Interfering; D008941:Spindle Apparatus / Q000378:metabolism; D025521:Tumor Suppressor Proteins / Q000235:genetics / Q000378:metabolism / Q000502:physiology*
D018797:Cell Cycle Proteins; D002868:Chromosomal Proteins, Non-Histone; D003598:Cytoskeletal Proteins; C120529:NDC80 protein, human; D009687:Nuclear Proteins; C440808:PINX1 protein, human; D034741:RNA, Small Interfering; D025521:Tumor Suppressor Proteins; C068688:centromere protein E