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lüll Sumoylation and the function of CCAAT enhancer binding protein alpha (C/EBP alpha) Khanna-Gupta ABlood Cells Mol Dis 2008[Jul]; 41 (1): 77-81CCAAT enhancer binding protein alpha (C/EBP alpha) is the founding member of a family of basic region/leucine zipper (bZIP) transcription factors and is a master regulator of granulopoiesis. It is expressed at high levels throughout myeloid differentiation and binds to the promoters of multiple myeloid-specific genes at different stages of myeloid maturation. Profound hematopoietic abnormalities occur in mice nullizygous for C/EBP alpha including a selective early block in the differentiation of granulocytes. Mutations in C/EBP alpha are present in a subset of patients with AML presenting with a normal karyotype. These mutations can result in the expression of a 30 kDa dominant negative C/EBP alpha isoform, which contributes to loss of C/EBP alpha function. The molecular basis for this observation remains unknown. In addition to phosphorylation, C/EBP alpha is modified, post-translationally by a small ubiquitin-related modifier (SUMO) at a lysine residue (K159), which lies within the growth inhibitory region of the C/EBP alpha protein. Sumoylation at K159 in the C/EBP alpha protein prevents association of the SWI/SNF chromatin remodeling complex with C/EBP alpha, thereby hampering transactivation. In this review, the functional implications of post-translational modification, particularly sumoylation, of C/EBP alpha in normal granulopoiesis and leukemia are considered.|*Myelopoiesis[MESH]|Animals[MESH]|CCAAT-Enhancer-Binding Protein-alpha/genetics/*metabolism[MESH]|Humans[MESH]|Leukemia, Myeloid, Acute/genetics/*metabolism[MESH]|Mutation[MESH]|Phosphorylation[MESH]|Protein Processing, Post-Translational[MESH]|Signal Transduction[MESH]|Small Ubiquitin-Related Modifier Proteins/*metabolism[MESH]|Transcriptional Activation[MESH] |