Cell cycle inhibition mediated by the outer surface of the C/EBPalpha basic region is required but not sufficient for granulopoiesis.
CCAAT/enhancer binding protein alpha (C/EBPalpha) transactivates target genes dependent upon DNA binding via its basic region-leucine zipper domain and slows G1 progression by interaction with E2F, cdk2, or cdk4. E2F interacts with the non-DNA-binding surface of the C/EBPalpha basic region and C/EBP...
| Main Authors: | , , , , |
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| Format: | Journal article |
| Language: | English |
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2003
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| _version_ | 1826262360250122240 |
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| author | Wang, Q Cleaves, R Kummalue, T Nerlov, C Friedman, A |
| author_facet | Wang, Q Cleaves, R Kummalue, T Nerlov, C Friedman, A |
| author_sort | Wang, Q |
| collection | OXFORD |
| description | CCAAT/enhancer binding protein alpha (C/EBPalpha) transactivates target genes dependent upon DNA binding via its basic region-leucine zipper domain and slows G1 progression by interaction with E2F, cdk2, or cdk4. E2F interacts with the non-DNA-binding surface of the C/EBPalpha basic region and C/EBPalpha residues 1-70 are required for repressing E2F targets, while cdk2 and cdk4 bind residues 177-191. C/EBPalpha-ER induces the 32D cl3 myeloblast cell line to differentiate to granulocytes. C/EBPalpha-ER variants incapable of binding DNA slowed G1, but did not induce early or late granulopoiesis, indicating that cell cycle inhibition as mediated by C/EBPalpha is not sufficient for differentiation. C/EBPalpha-ER variants lacking residues 11-70 or residues 11-70 and 178-200 both slowed the G1 to S transition. C/EBPalpha(GZ)-ER, containing the GCN4 rather than the C/EBPalpha leucine zipper, also slowed G1. In contrast, C/EBPalpha(BRM2)-ER, carrying mutations in the outer surface of the basic region required for interaction with E2F, did not slow G1. C/EBPalpha(BRM2)-ER induced early markers of granulopoiesis much less efficiently than C/EBPalpha-ER and did not direct terminal maturation. Inhibition of G1 progression using mimosine increased induction of late markers by G-CSF. Thus, both DNA binding and cell cycle arrest, mediated by opposite surfaces of the C/EBPalpha basic region, are required for granulopoiesis. |
| first_indexed | 2024-03-06T19:35:12Z |
| format | Journal article |
| id | oxford-uuid:1eced88d-e8c6-4696-86ea-6b6d7455ed55 |
| institution | University of Oxford |
| language | English |
| last_indexed | 2024-03-06T19:35:12Z |
| publishDate | 2003 |
| record_format | dspace |
| spelling | oxford-uuid:1eced88d-e8c6-4696-86ea-6b6d7455ed552022-03-26T11:18:25ZCell cycle inhibition mediated by the outer surface of the C/EBPalpha basic region is required but not sufficient for granulopoiesis.Journal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:1eced88d-e8c6-4696-86ea-6b6d7455ed55EnglishSymplectic Elements at Oxford2003Wang, QCleaves, RKummalue, TNerlov, CFriedman, ACCAAT/enhancer binding protein alpha (C/EBPalpha) transactivates target genes dependent upon DNA binding via its basic region-leucine zipper domain and slows G1 progression by interaction with E2F, cdk2, or cdk4. E2F interacts with the non-DNA-binding surface of the C/EBPalpha basic region and C/EBPalpha residues 1-70 are required for repressing E2F targets, while cdk2 and cdk4 bind residues 177-191. C/EBPalpha-ER induces the 32D cl3 myeloblast cell line to differentiate to granulocytes. C/EBPalpha-ER variants incapable of binding DNA slowed G1, but did not induce early or late granulopoiesis, indicating that cell cycle inhibition as mediated by C/EBPalpha is not sufficient for differentiation. C/EBPalpha-ER variants lacking residues 11-70 or residues 11-70 and 178-200 both slowed the G1 to S transition. C/EBPalpha(GZ)-ER, containing the GCN4 rather than the C/EBPalpha leucine zipper, also slowed G1. In contrast, C/EBPalpha(BRM2)-ER, carrying mutations in the outer surface of the basic region required for interaction with E2F, did not slow G1. C/EBPalpha(BRM2)-ER induced early markers of granulopoiesis much less efficiently than C/EBPalpha-ER and did not direct terminal maturation. Inhibition of G1 progression using mimosine increased induction of late markers by G-CSF. Thus, both DNA binding and cell cycle arrest, mediated by opposite surfaces of the C/EBPalpha basic region, are required for granulopoiesis. |
| spellingShingle | Wang, Q Cleaves, R Kummalue, T Nerlov, C Friedman, A Cell cycle inhibition mediated by the outer surface of the C/EBPalpha basic region is required but not sufficient for granulopoiesis. |
| title | Cell cycle inhibition mediated by the outer surface of the C/EBPalpha basic region is required but not sufficient for granulopoiesis. |
| title_full | Cell cycle inhibition mediated by the outer surface of the C/EBPalpha basic region is required but not sufficient for granulopoiesis. |
| title_fullStr | Cell cycle inhibition mediated by the outer surface of the C/EBPalpha basic region is required but not sufficient for granulopoiesis. |
| title_full_unstemmed | Cell cycle inhibition mediated by the outer surface of the C/EBPalpha basic region is required but not sufficient for granulopoiesis. |
| title_short | Cell cycle inhibition mediated by the outer surface of the C/EBPalpha basic region is required but not sufficient for granulopoiesis. |
| title_sort | cell cycle inhibition mediated by the outer surface of the c ebpalpha basic region is required but not sufficient for granulopoiesis |
| work_keys_str_mv | AT wangq cellcycleinhibitionmediatedbytheoutersurfaceofthecebpalphabasicregionisrequiredbutnotsufficientforgranulopoiesis AT cleavesr cellcycleinhibitionmediatedbytheoutersurfaceofthecebpalphabasicregionisrequiredbutnotsufficientforgranulopoiesis AT kummaluet cellcycleinhibitionmediatedbytheoutersurfaceofthecebpalphabasicregionisrequiredbutnotsufficientforgranulopoiesis AT nerlovc cellcycleinhibitionmediatedbytheoutersurfaceofthecebpalphabasicregionisrequiredbutnotsufficientforgranulopoiesis AT friedmana cellcycleinhibitionmediatedbytheoutersurfaceofthecebpalphabasicregionisrequiredbutnotsufficientforgranulopoiesis |