TLE family member 5, transcriptional modulator (TLE5)

TLE family member 5, also known as TLE5 or Amino-terminal enhancer of split (AES), is a member of the Groucho/transducin-like enhancer of split (TLE) family of transcriptional corepressors[1][2][4]. Unlike the long TLE family members (TLE1–4), TLE5 is a short isoform lacking the WD repeat domain and functions primarily as a dominant negative regulator by binding to the Q domain of long TLE proteins and preventing tetramer formation, thus modulating their ability to repress target gene expression[1]. TLE5 also has independent roles: it participates in the negative regulation of NF-κB and androgen receptor target gene expression, modulates Wnt and Notch signaling pathways, and is essential for proper cell fate determination and differentiation. Loss of TLE5 function has been linked to enhanced tumor invasiveness and metastasis in several cancers and is associated with drug resistance[1][4]. No drugs are currently available that directly target TLE5, but inhibitors of related signaling pathways may modulate its activity or stability in disease contexts.

Other names

AESAmino-terminal enhancer of splitGRG5Groucho-related protein 5ESP1Gp130-associated protein GAMProtein GRGProtein ESP1TLE5Amino enhancer of splitGRGAES-1AES-2TLE family member 5amino-terminal enhancer of split

Dominant negative inhibition of long TLE members (suppresses TLE tetramer formation); corepression of gene expression via interaction with transcription factors (e.g., TCF/LEF1 in Wnt pathway, HES1 in Notch, and AR in androgen signaling); recruitment (or interference with recruitment) of HDACs for transcriptional suppression[1][2][4]