Octamer-binding transcription factor 4–SRY-box transcription factor 2–Kruppel-like factor 4 protein complex (OSK complex)

The Octamer-binding transcription factor 4–SRY-box transcription factor 2–Kruppel-like factor 4 (OSK) protein complex is a master regulatory assembly essential for the induction and maintenance of pluripotency in mammalian cells (Takahashi & Yamanaka, 2006). Comprising the transcription factors POU5F1 (Oct4), SOX2, and KLF4, this complex cooperatively binds to specific regulatory elements, such as enhancers and promoters, to drive the expression of genes required for stem cell self-renewal while repressing differentiation-linked genes (Boyer et al., 2005). In regenerative medicine, the OSK complex is the primary driver used to reprogram somatic cells into induced pluripotent stem cells (iPSCs), offering potential treatments for various degenerative conditions and even reversing aging-related cellular phenotypes in vivo (Lu et al., 2020). However, dysregulation of these factors is frequently observed in many cancers, where they contribute to the maintenance of cancer stem cell populations and promote tumor aggressiveness and chemoresistance (Malik et al., 2019). Therapeutic strategies targeting the OSK complex include small molecule modulators to enhance reprogramming efficiency or inhibitors to disrupt cancer stem cell survival. A significant challenge in targeting this complex is the risk of teratoma formation and the potential for unintended oncogenic transformation due to the potent proliferative signals these factors induce (Knoepfler, 2009).

Other names

OSKYamanaka factors (subset)POU5F1–SOX2–KLF4 complexPluripotency-associated transcription factor complexOct4-Sox2-Klf4 enhanceosome

Cooperative DNA binding to pluripotency enhancers and recruitment of chromatin remodeling complexes to activate stemness genes and repress differentiation genes.