CEBPalpha

CEBPalpha, also known as CCAAT/enhancer-binding protein alpha, is a basic leucine zipper transcription factor encoded by the CEBPA gene in humans. It belongs to the C/EBP family, which regulates differentiation and metabolism across multiple tissues. C/EBPα binds DNA as a dimer, typically recognizing CCAAT/enhancer elements, and can form homodimers or heterodimers with other C/EBP members. The protein contains an N-terminal transactivation domain and a C-terminal basic region followed by a leucine zipper that mediates dimerization and DNA binding.

Two major protein isoforms arise from alternative translation initiation: the full-length p42-CEBPα and the truncated p30-CEBPα. The p42 isoform generally promotes normal myeloid differentiation and hepatocyte function, whereas the p30 isoform lacks part of the transactivation domain and can have distinct regulatory effects, including altered transcriptional activity that can contribute to leukemogenesis in certain contexts.

Biological roles of C/EBPα are broad. It is essential for granulocyte and monocyte differentiation in hematopoiesis and plays a key role in adipogenesis, promoting the conversion of preadipocytes to adipocytes. It also participates in liver development and metabolism, cooperating with other transcription factors such as C/EBPβ and PPARγ to regulate genes involved in glucose and lipid metabolism. Regulation occurs at transcriptional and post-transcriptional levels, with activity modulated by phosphorylation and interactions with coactivators like CBP/p300.

Clinical significance includes its involvement in acute myeloid leukemia (AML). CEBPA mutations are found in a subset of AML cases, often affecting the N-terminus to favor the p30 isoform, or combining N- and C-terminal alterations. Biallelic CEBPA mutations are associated with a relatively favorable prognosis in AML and influence treatment response.