Nuclear Phosphatase Regulates Proteasome Activity

A recent paper described the discovery of a proteasome phosphatase that regulates the removal of unnecessary or damaged proteins from cells by modulating the activity of the 26S proteasome.

The ubiquitin-proteasome system (UPS) is the mechanism by which malfunctioning and possibly toxic proteins are removed from the cell. This system is based on the tagging of damaged proteins with ubiquitin, and the digestion of the subsequent ubiquinated proteins by the proteasome. In the current study investigators at the University of California, San Diego (USA) and the University of California, Irvine have shed new light on the molecular mechanism that controls proteasome activity.

They reported in the September 26, 2011, online edition of the journal Proceedings of the [US] National Academy of Sciences that a 26S proteasome phosphatase called ubiquitin-like domain-containing C-terminal domain phosphatase 1 (UBLCP1) regulated nuclear proteasome activity. UBLCP1 dephosphorylated the 26S proteasome and inhibited proteasome activity in vitro. Knockdown of UBLCP1 in cells promoted 26S proteasome assembly and selectively enhanced nuclear proteasome activity. UBLCP1 directly interacted with the proteasome via its UBL domain and it was exclusively localized in the nucleus.

“So far, UBLCP1 is the only proteasome-specific phosphatase identified to exist in mammalian cells,” said senior author Dr. Jack E. Dixon professor of pharmacology, cellular, and molecular medicine at the University of California, San Diego. “We are just beginning to understand how it alters proteasome activity, but one can anticipate that defects in the phosphatase activity are likely to result in major alterations in the ability of the cell to remove damaged protein.”

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University of California, San Diego
University of California, Irvine