Heat shock protein is a unique marker of growth arrest during macrophage differentiation of HL-60 cells.
Prior to morphologic and functional maturation, terminally differentiating hematopoietic cells first exit the cell cycle and undergo growth arrest. Relatively little is known about which molecules regulate differentiation-induced growth arrest. In the present report, we sought to determine whether the mammalian low molecular weight heat shock protein (hsp28) was a candidate growth-regulatory molecule during human hematopoiesis. To this end, hsp28 protein expression was examined during phorbol ester (PMA)-induced macrophage differentiation of the human HL-60 promyelocytic leukemic cell line. Whereas hsp28 was constitutively expressed at relatively low levels in an unphosphorylated state, hsp28 was rapidly phosphorylated within 4 hr following PMA-induced differentiation, preceding increased hsp28 protein levels at 24-48 h. In contrast to other differentiative agents, hsp28 steady state mRNA and protein were regulated concordantly in response to macrophage differentiation. More importantly, these changes were transient, and occurred concomitant with the down-regulation of cellular proliferation and the onset of G1 phase cell cycle arrest. In total, these observations implicate hsp28 as an intermediary in the myelomonocytic differentiative pathway of promyelocytic leukemic cells, and will shed light on the events regulating this process.
Spector
N L
NL
Division of Tumor Immunology, Dana-Farber Cancer Institute, Boston, Massachusetts 02115.
Ryan
C
C
Samson
W
W
Levine
H
H
Nadler
L M
LM
Arrigo
A P
AP
D015415:Biomarkers; D002454:Cell Differentiation; D002455:Cell Division; D006360:Heat-Shock Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D006706:Homeostasis; D006801:Humans; D015473:Leukemia, Promyelocytic, Acute / Q000378:metabolism* / Q000473:pathology*; D008264:Macrophages / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology*; D008970:Molecular Weight; D010766:Phosphorylation; D012333:RNA, Messenger / Q000378:metabolism; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D014407:Tumor Cells, Cultured
D015415:Biomarkers; D006360:Heat-Shock Proteins; D012333:RNA, Messenger; D013755:Tetradecanoylphorbol Acetate