URI1

This gene encodes member of the prefoldin family of molecular chaperones. The encoded protein functions as a scaffolding protein and plays roles in ubiquitination and transcription, in part though interactions with the RNA polymerase II subunit RPB5. This gene may play a role in multiple malignancies including ovarian cancer and hepatocellular carcinoma. Alternatively spliced transcript variants encoding multiple isoforms have been observed for this gene, and a pseudogene of this gene is located on the long arm of chromosome 22. [provided by RefSeq, Nov 2011]

Full Name

URI1, Prefoldin Like Chaperone

Function

Involved in gene transcription regulation. Acts as a transcriptional repressor in concert with the corepressor UXT to regulate androgen receptor (AR) transcription. May act as a tumor suppressor to repress AR-mediated gene transcription and to inhibit anchorage-independent growth in prostate cancer cells. Required for cell survival in ovarian cancer cells. Together with UXT, associates with chromatin to the NKX3-1 promoter region. Antagonizes transcriptional modulation via hepatitis B virus X protein.
Plays a central role in maintaining S6K1 signaling and BAD phosphorylation under normal growth conditions thereby protecting cells from potential deleterious effects of sustained S6K1 signaling. The URI1-PPP1CC complex acts as a central component of a negative feedback mechanism that counteracts excessive S6K1 survival signaling to BAD in response to growth factors. Mediates inhibition of PPP1CC phosphatase activity in mitochondria. Coordinates the regulation of nutrient-sensitive gene expression availability in a mTOR-dependent manner. Seems to be a scaffolding protein able to assemble a prefoldin-like complex that contains PFDs and proteins with roles in transcription and ubiquitination.

Biological Process

Biological Process cellular response to growth factor stimulus Source:UniProtKB1 Publication
Biological Process cellular response to steroid hormone stimulus Source:UniProtKB1 Publication
Biological Process negative regulation of intrinsic apoptotic signaling pathway Source:UniProtKB1 Publication
Biological Process negative regulation of phosphatase activity Source:UniProtKB1 Publication
Biological Process negative regulation of transcription by RNA polymerase II Source:UniProtKB3 Publications
Biological Process protein stabilization Source:ComplexPortal2 Publications
Biological Process regulation of cell growth Source:UniProtKB1 Publication
Biological Process regulation of transcription by RNA polymerase II Source:UniProtKB1 Publication
Biological Process response to virus Source:UniProtKB1 Publication

Cellular Location

Nucleus
Cytoplasm
Mitochondrion
Cell projection, dendrite
Colocalizes with PFDN2, PFDN4, PPP1CC, RPS6KB1 and STAP1 at mitochondrion.

PTM

Phosphorylated. Phosphorylation occurs essentially on serine residues. Phosphorylation occurs in response to androgen treatment in prostate cancer cells in a mTOR-dependent manner. Phosphorylated; hyperhosphorylated in mitochondria in a mTORC-dependent signaling pathway. Phosphorylated at Ser-372 by RPS6KB1 in a growth factor- and rapamycin-dependent manner. S6K1-mediated mitochondrial phosphorylation at Ser-372 disrupts the URI1-PPP1CC complex in the mitochondrion, relieves PPP1CC phosphatase inhibition activity and hence engages a negative feedback diminishing RPS6KB1 kinase activity, preventing sustained S6K1-dependent signaling.