Overexpression of SPINDLIN1 induces cellular senescence, multinucleation and apoptosis.
Human or mouse Spindlin1 is expressed in various tissues and cells, but its biological functions are poorly understood. In this study, we show that human SPINDLIN1 is localized to interphase nucleus and mitotic chromosomes, and its expression in HeLa cells is not regulated in a cell cycle-dependent manner. When SPINDLIN1 is stably overexpressed in HeLa cells, it results in multinucleation of cells, and these multinucleated cells exhibits characteristic features of senescence and apoptosis shown by growth and morphological alterations, beta-galactosidase activity, and Annexin V/7-Aminoactinomycin D staining. Mouse Spindlin1 is highly homologous with human Spindlin1, when overexpressed in NIH3T3 cells, it also induces multinucleation, senescence and apoptosis in murine cells. Our results demonstrate that SPINDLIN1 is an important gene for mammalian mitotic chromosome functions, and disrupted regulation results in abnormal cell division, a mechanism that may be involved in tumorigenesis.
Yuan
Hongfeng
H
Laboratory of Stem Cell and Regeneration Medicine, Beijing Institute of Transfusion Medicine, 27 Taiping Road, Beijing, China.
Zhang
Peng
P
Qin
Lipeng
L
Chen
Lin
L
Shi
Shuangshuang
S
Lu
Yang
Y
Yan
Fang
F
Bai
Cixian
C
Nan
Xue
X
Liu
Daqing
D
Li
Yanhua
Y
Yue
Wen
W
Pei
Xuetao
X
D000595:Amino Acid Sequence; D000818:Animals; D017209:Apoptosis / Q000235:genetics*; D018797:Cell Cycle Proteins / Q000737:chemistry / Q000235:genetics*; D016922:Cellular Senescence / Q000235:genetics*; D006367:HeLa Cells; D006801:Humans; D051379:Mice; D008869:Microtubule-Associated Proteins / Q000737:chemistry / Q000235:genetics*; D008969:Molecular Sequence Data; D041681:NIH 3T3 Cells; D010750:Phosphoproteins / Q000737:chemistry / Q000235:genetics*; D017386:Sequence Homology, Amino Acid
D018797:Cell Cycle Proteins; D008869:Microtubule-Associated Proteins; D010750:Phosphoproteins; C104434:spindlin