Abstract / Summary
Myeloid/Lymphoid or Mixed-Lineage Leukemia Translocated to 1 (MLLT1), also known as ENL, is a critical chromatin-associated protein within the super elongation complex (SEC) that regulates transcriptional elongation and is frequently implicated in leukemias and Wilms tumor through fusions and mutations. Despite its oncogenic roles, the phosphoregulatory mechanisms of MLLT1 remain underexplored. This study integrates large-scale phosphoproteomic datasets to identify predominant phosphosites (S292, S359, S361) on MLLT1 and delineate their co-phosphoregulated protein networks using Fisher’s Exact Test, Gene Ontology enrichment, and interaction databases. Results reveal a network enriched in chromatin remodeling, histone binding, transcription elongation via SEC and PAF complexes, RNA processing, and genome stability, with S292 emerging as a significant phosphorylation site. Upstream kinases, such as CDK9, and binary interactors, including KMT2A and DOT1L, underscore MLLT1’s integration of phosphorylation with epigenetic control. Cancer associations link these phosphosites to leukemia, Wilms tumor, and potentially lung cancers, highlighting novel therapeutic avenues. This analysis provides mechanistic insights into MLLT1’s phosphoregulated functions in transcriptional control and oncogenesis.