Apoptosis related protein 3, an ATRA-upregulated membrane protein arrests the cell cycle at G1/S phase by decreasing the expression of cyclin D1.
Human Apr3 was first cloned from HL-60 cells treated by ATRA. In this study, we further demonstrated that Apr3 could be obviously upregulated by ATRA in many other ATRA sensitive cells, suggesting a common role of Apr3 in ATRA effects. Indirect immunofluorescence assay indicates that Apr3 is a membrane protein, while its truncated form without the predicted transmembrane and intracellular domain, was likely a secreted one. Furthermore, FACS analysis showed that Apr3 overexpression could cause an obvious G1/S phase arrest which might be induced by dramatic reduction of cyclin D1 expression. Strikingly, the truncated Apr3 antagonized the negative role of Apr3 on cell cycle and cyclin D1. Taken together, our data suggest that Apr3 should play an important role in ATRA signal pathway and the predicted transmembrane and/or the intracellular domain mediates Apr3 membrane localization and is vital for the negative regulation on cell cycle and cyclin D1.
Yu
Fang
F
Department of Biochemistry and Molecular Biology, The State Key Laboratory of Cancer Biology, The Fourth Military Medical University, Xi'an 710032, PR China.
Yang
Guodong
G
Zhao
Zhongliang
Z
Ji
Lin
L
Cao
Yunxin
Y
Bai
Liyuan
L
Lu
Fan
F
Fu
Haiyan
H
Huang
Bo
B
Li
Hua
H
Zhang
Jie
J
Yao
Libo
L
Lu
Zifan
Z
D051378:Actin-Related Protein 3 / Q000378:metabolism*; D002453:Cell Cycle / Q000187:drug effects / Q000502:physiology*; D056741:Cyclin D; D016213:Cyclins / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D015536:Down-Regulation / Q000187:drug effects / Q000502:physiology; D005786:Gene Expression Regulation / Q000187:drug effects / Q000502:physiology*; D018922:HL-60 Cells; D006801:Humans; D014212:Tretinoin / Q000008:administration & dosage*; D015854:Up-Regulation / Q000187:drug effects / Q000502:physiology
D051378:Actin-Related Protein 3; D056741:Cyclin D; D016213:Cyclins; D014212:Tretinoin