Ring1-flox Mouse

Ring1, also known as ring finger protein 1, is an essential component of the polycomb-group proteins. It is a catalytic subunit within Polycomb repressive complex 1 (PRC1) along with RNF2, and modifies chromatin through catalyzing histone H2A lysine 119 monoubiquitination (H2AK119ub1). It is involved in various biological processes such as development, cell cycle regulation, and DNA damage repair, and is associated with multiple signaling pathways like Wnt/β-catenin and Notch signaling [1,2,6].

In neurogenesis, hypomorphic RING1 in neural progenitor cells (NPCs) leads to reduced H2AK119ub1, causing delayed DNA damage repair and cell cycle progression, while not significantly impacting NPC differentiation [1]. In the context of forelimb bud development, depletion of RING1A and RING1B (essential PRC1 components) results in severe forelimb formation defects along the proximal-distal (PD) axis due to failure in repressing proximal signal circuitry including Meis2 [3]. In hepatic progenitor cells (HPCs), overexpression of Ring1 promotes their transformation into cancer stem-like cells via the Wnt/β-catenin signaling pathway [2]. In non-small cell lung cancer, high expression of RING1 is associated with poor prognosis, and its knockdown suppresses cell growth through G1/S cell cycle arrest [4]. In breast cancer, low RING1 expression is an unfavorable prognostic factor [5].

In conclusion, Ring1 is crucial for multiple biological processes, including neurogenesis, limb development, and cell differentiation. Its role in diseases such as non-small cell lung cancer and breast cancer, as revealed by functional studies including gene knockout-related models, emphasizes its potential as a biomarker and therapeutic target in cancer research.