Overexpression of a novel osteopetrosis-related gene CCDC154 suppresses cell proliferation by inducing G2/M arrest.
Osteopetrosis, a disorder of skeletal bone, can cause death during childhood. We previously described a new spontaneous autosomal recessive osteopetrosis mouse mutant, "new toothless" (ntl). In this study, we reported for the first time the identification, cloning and characterization of the coiled-coil domain-containing 154 (CCDC154), a novel gene whose deletion of ~5 kb sequence including exons 1-6 was completely linked to the ntl mutant. The CCDC154 was conserved between mouse and human and is wildly expressed in mouse tissues. The cellular localization of CCDC154 was in the early endosomes. Overexpression of CCDC154 inhibited cell proliferation of HEK293 cells by inducing G 2/M arrest. CCDC154 also inhibited tumor cell growth, and the soft agar assay revealed a significant decrease of the colony size of Hela cells upon transfection of CCDC154. Our results indicate that CCDC154 is a novel osteopetrosis-related gene involved in cell cycle regulation and tumor suppression growth.
Institute of Genomic Medicine, Wenzhou Medical College, Wenzhou, China.
Wanqin
W
Liao
Rongsen
R
Zhao
Liting
L
Lu
Rongrong
R
Zhang
Jiawei
J
Zou
Tao
T
Xu
Changjie
C
Wu
Jiajia
J
Tang
Yuezhen
Y
Deng
Xincheng
X
Lu
D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D018797:Cell Cycle Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D049109:Cell Proliferation; D017931:DNA Primers / Q000235:genetics; D011992:Endosomes / Q000378:metabolism; D059565:G2 Phase Cell Cycle Checkpoints / Q000235:genetics / Q000502:physiology*; D057809:HEK293 Cells; D006367:HeLa Cells; D006801:Humans; D051379:Mice; D008856:Microscopy, Fluorescence; D008958:Models, Molecular; D008969:Molecular Sequence Data; D010022:Osteopetrosis / Q000235:genetics / Q000378:metabolism*; D016133:Polymerase Chain Reaction; D017422:Sequence Analysis, DNA; D025521:Tumor Suppressor Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*
C577149:CCDC154 protein, human; D018797:Cell Cycle Proteins; D017931:DNA Primers; D025521:Tumor Suppressor Proteins