ADRM1

ADRM1 Full Name

adhesion regulating molecule 1

ADRM1 Introduction

Adhesion regulating molecule 1 (ADRM1), most predominantly recognized in molecular biology as Rpn13, is a critical ubiquitin receptor seamlessly integrated into the 19S regulatory particle of the 26S proteasome. Structurally, it features a highly specialized Pleckstrin-like receptor for ubiquitin (Pru) domain. The primary physiological function of ADRM1 is to act as a dynamic docking station for polyubiquitinated proteins slated for cellular destruction. By binding directly to ubiquitin chains and simultaneously recruiting the deubiquitinating enzyme UCHL5 (also known as UCH37), ADRM1 elegantly couples target substrate recognition with the necessary deubiquitination step just prior to protein degradation. This sophisticated molecular machinery is absolutely vital for maintaining cellular protein homeostasis (proteostasis); it continuously clears out damaged, misfolded, or obsolete proteins, thereby preventing toxic cellular accumulation.

Figure 1. A Surface Opposite RPN13 Ubiquitin-Binding Loops Is Implicated in RA190 Binding. (Source: Anchoori RK, et al. 2013)

Clinically, the dysregulation of ADRM1 is most prominently linked to the pathogenesis and progression of severe malignancies. Because rapidly dividing cancer cells inevitably produce abnormally high levels of misfolded proteins due to genomic instability, they become exceptionally reliant on hyperactive proteasomal clearance to survive. Consequently, ADRM1 is significantly overexpressed in a wide spectrum of aggressive solid tumors and hematological malignancies, including ovarian cancer, gastric cancer, and multiple myeloma. Within the tumor microenvironment, robust ADRM1 expression actively drives tumor proliferation, metastasis, and resistance to standard apoptotic signals by rapidly clearing tumor suppressor proteins. Because it represents a highly specialized structural bottleneck in the cancer cell's waste disposal system, ADRM1 has rapidly emerged as an exceptionally promising target for novel anti-cancer therapeutics. The targeted pharmacological inhibition or genetic silencing of ADRM1 creates a fatal "traffic jam" at the proteasome. This induces rapid, catastrophic proteotoxic stress exclusively in malignant cells, offering a highly potent strategy to combat chemoresistant cancers while potentially sparing healthy, slower-dividing tissues.

Alternate Names for ADRM1

ADRM1; adhesion regulating molecule 1; proteasomal ubiquitin receptor ADRM1; ARM1; GP110; Rpn13; ARM-1; hRpn13; rpn13 homolog; M(r) 110,000 surface antigen

• 1. Anchoori RK, et al. A bis-benzylidine piperidone targeting proteasome ubiquitin receptor RPN13/ADRM1 as a therapy for cancer. Cancer Cell. 2013 Dec 9;24(6):791-805.
  2. Liang YC, et al. ADRM1 as a therapeutic target in hepatocellular carcinoma. Kaohsiung J Med Sci. 2021 Jan;37(1):47-54.