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Distinct involvement of cAMP‐response element‐dependent transcriptions in functional and morphological maturation during retinoid‐mediated human myeloid differentiation
Author(s) -
Saeki Kumiko,
Saeki Koichi,
Yuo Akira
Publication year - 2003
Publication title -
journal of leukocyte biology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.819
H-Index - 191
eISSN - 1938-3673
pISSN - 0741-5400
DOI - 10.1189/jlb.1002512
Subject(s) - creb , biology , transcription factor , cellular differentiation , retinoic acid , microbiology and biotechnology , cyclic amp response element binding protein , response element , enhancer , gene expression , cell culture , biochemistry , promoter , genetics , gene
We evaluated the involvement of cyclic adenosine monophosphate‐response element (CRE)‐dependent transcriptions in all‐trans retinoic acid (ATRA)‐induced myeloid differentiation using human monoblastic U937 cells. ATRA treatment caused an increment in the CRE‐dependent transcription activity and induced a wide variety of differentiation phenotypes including functional and morphological maturation. Indeed, ATRA treatment induced the expression of CCAAT/enhancer‐binding protein β (C/EBPβ), a CRE‐dependent transcription factor important in monocytic differentiation, and the inhibition of CRE‐enhancer activity by the expression of a dominant‐negative CRE‐binding protein (dn‐CREB) abolished the induction of C/EBPβ. Functional maturation, such as the enhancement of cell adhesion and respiratory burst activity, was dramatically suppressed by the expression of dn‐CREB. In addition, the differentiation‐dependent induction of an adhesion molecule (CD11b), the phagocyte oxidase required for respiratory burst, and the transcription factor PU.1 responsible for phagocyte oxidase induction were all abolished by dn‐CREB. Surprisingly, morphological maturation, including nuclear convolution and ctoplasmic vacuolar formation, was augmented by dn‐CREB. Under the same conditions, the differentiation‐associated cell‐growth arrest was not affected by the expression of dn‐CREB. Our results clearly indicate that CRE‐driven transcription plays at least three distinct roles during myeloid differentiation: It stimulates functional maturation but suppresses morphological maturation and has no effects on cell‐growth arrest.