L-myc-1 proto-oncogene protein (MYCL) (MYCL)

L-myc-1 proto-oncogene protein (MYCL) is a member of the MYC family of basic helix-loop-helix leucine zipper (bHLH-LZ) transcription factors, which also includes c-MYC and N-MYC [1, 15]. It functions as a nuclear transcription factor that heterodimerizes with the MAX protein to bind E-box DNA sequences, thereby regulating the expression of genes critical for cell cycle progression, metabolism, and apoptosis [3, 13]. While L-MYC expression is highly restricted in most adult tissues, it is frequently amplified or overexpressed in specific cancers, particularly small cell lung cancer (SCLC) and Merkel cell carcinoma, where it acts as a potent driver of oncogenesis and therapeutic resistance [2, 4, 14]. Beyond its role in cancer, L-MYC is involved in normal physiological processes such as the regulation of inner ear auditory receptor cell differentiation and has been shown to promote induced pluripotent stem cell (iPSC) reprogramming with high efficiency [1, 2, 11]. Historically considered 'undruggable' due to its intrinsically disordered structure and lack of a traditional small-molecule binding pocket, L-MYC is now a focal point for novel therapeutic strategies [12, 16]. These include mini-proteins like Omomyc that disrupt MYC-MAX dimerization, BET bromodomain inhibitors that suppress MYCL transcription, and molecular glue degraders specifically evaluated in L-MYC-amplified tumors [4, 12, 14].

Other names

MYCL1LMYCbHLHe38L-Mycv-myc avian myelocytomatosis viral oncogene lung carcinoma derived homologProtein L-Myc-1Class E basic helix-loop-helix protein 38Myc-related gene from lung cancer

Inhibition of MYC-MAX dimerization, downregulation of MYC transcription via BET or CDK9 inhibition, targeted protein degradation via molecular glues, and stabilization of MAX-MAX homodimers.