PSMD10

PSMD10 (Proteasome 26S Subunit, Non-ATPase 10), also known as gankyrin, is a protein that in humans is encoded by the PSMD10 gene. This protein is a non-ATPase subunit of the 19S regulator lid of the 26S proteasome, which is involved in the ATP-dependent degradation of ubiquitinated proteins. The 26S proteasome is a multicatalytic proteinase complex with a highly ordered structure composed of two complexes, a 20S core and a 19S regulator. The 20S core is composed of 4 rings of 28 non-identical subunits; 2 rings are made up of 7 alpha subunits and 2 rings are made up of 7 beta subunits. The 19S regulator is composed of a base, which contains 6 ATPase subunits and 2 non-ATPase subunits, and a lid, which contains up to 10 non-ATPase subunits. PSMD10 is one of the non-ATPase subunits that compose the lid of the 19S regulatory particle of the 26S proteasome.

Function

PSMD10 is implicated in the regulation of cell proliferation and apoptosis. It has been identified as an oncoprotein in several types of cancers, including liver, gastric, and hepatocellular carcinomas. PSMD10 overexpression is associated with the progression of these cancers and poor prognosis. The protein interacts with several key cellular regulators including the tumor suppressor protein p53, and is involved in the control of the cell cycle and cell growth. By regulating the degradation of specific target proteins, PSMD10 plays a crucial role in maintaining cellular homeostasis.

Clinical Significance

The role of PSMD10 in cancer has made it a potential target for cancer therapy. Inhibitors targeting PSMD10 are being explored as therapeutic options to halt the progression of tumors where PSMD10 is found to be overexpressed. Additionally, PSMD10's interaction with p53 suggests that modulation of PSMD10 activity could influence p53-mediated pathways, offering another avenue for therapeutic intervention in cancers where p53 is mutated or inactivated.

Molecular Biology

The PSMD10 gene is located on the short (p) arm of chromosome X at position 22.2, spanning approximately 17 kb of DNA and consisting of 9 exons. The PSMD10 protein has a molecular weight of approximately 28 kDa and is ubiquitously expressed in various tissues. Its structure includes several conserved domains that are critical for its function within the proteasome and its interaction with other proteins.

Research Directions

Ongoing research is focused on elucidating the detailed mechanisms by which PSMD10 contributes to tumorigenesis and identifying other potential interacting partners of PSMD10 in the cell. Studies are also aimed at understanding how PSMD10 expression is regulated at the genetic and epigenetic levels. Furthermore, the development of specific inhibitors that can modulate the activity of PSMD10 is a key area of interest in the field of cancer therapeutics.