A Mutant Plasma Membrane Protein Is Stabilized Upon Loss of Yvh1, a Novel Ribosome Assembly Factor

Abstract

Pma1-10 is a mutant plasma membrane ATPase defective at the restrictive temperature in stability at the cell surface. At 37°, Pma1-10 is ubiquitinated and internalized from the plasma membrane for degradation in the vacuole. YVH1, encoding a tyrosine phosphatase, is a mutant suppressor of pma1-10 ; in the absence of Yvh1, Pma1-10 remains stable at the plasma membrane, thereby permitting cells to grow. The RING finger domain of Yvh1, but not its phosphatase domain, is required for removal of mutant Pma1-10 from the plasma membrane. Yvh1 is a novel ribosome assembly factor: in yvh1D cells, free 60S and 80S ribosomal subunits are decreased, free 40S subunits are increased, and half-mer polysomes are accumulated. Pma1-10 is also stabilized by deletion of 60S ribosomal proteins Rpl19a and Rpl35a. We propose that changes in ribosome biogenesis caused by loss of Yvh1 or specific ribosomal proteins have effects on the plasma membrane, perhaps by producing specific translational changes.

The dual-specificity phosphatase hYVH1 (DUSP12) is a novel modulator of cellular DNA content

“…In yeast, the C-terminal zinc-binding domain is able to complement the slow-growth phenotype of a yvh1 deletion, 8,16 rescue the 60S export defect 12,13,16 and is necessary for glycogen accumulation, growth and spore maturation. 8 In humans, this domain can function as a redox sensor and is necessary for the cytoprotective function of hYVH1.…”

The Atypical Dual Specificity Phosphatase hYVH1 Associates with Multiple Ribonucleoprotein Particles

“…We observed that both wild-type hYVH1 and hYVH1 C115S (a phosphatase-inactive mutant) co-immunoprecipitated YB-1 and FMRP to a similar extent, suggesting that phosphatase activity is likely not required to associate with YB-1 and FMRP particles. Regarding the modular domains of hYVH1, the ZBD of hYVH1 has been shown to be required, and in some instances sufficient, for the observed hYVH1-mediated cellular functions, such as ribosome biogenesis (11)(12)(13), cell cycle regulation (14), and cell survival (15). As shown in Fig.…”

“…Although the precise physiological role of hYVH1 remains uncharacterized, recent evidence indicates that YVH1 orthologs may be critical mediators of ribosome biogenesis (11)(12)(13), cell cycle regulation (14), and cell survival (15,16). Furthermore, the hyvh1 gene has been found to be significantly amplified in various cancers that have progressed to advanced stages (17)(18)(19), highlighting the importance of examining the biological activities of hYVH1.…”

Emerging Roles of Atypical Dual Specificity Phosphatases in Cancer

“…Defects within specific steps or association of proteins with defined complexes within this multistep process can be inferred from polysome analyses as each complex in endowed with a unique sedimentation coefficient within sucrose gradients [80]. Polysome analysis in yeast demonstrated that Yvh1p associates with pre-60S ribosomes and loss of YVH1 results in an increase in half-mers (consisting of a 48S small subunit that fails to join to a large 60S ribosomal subunit) [81]. The production of translationally incompetent half-mers likely results from defects in cytoplasmic 60S maturation [80,81].…”

“…Polysome analysis in yeast demonstrated that Yvh1p associates with pre-60S ribosomes and loss of YVH1 results in an increase in half-mers (consisting of a 48S small subunit that fails to join to a large 60S ribosomal subunit) [81]. The production of translationally incompetent half-mers likely results from defects in cytoplasmic 60S maturation [80,81]. In addition to specific temporal associations of initiation factors with the 40S subunit, the nuclear pre-60S subunits associate with Mrt4p, which is subsequently displaced by the P0/P1/P2 ribosomal stalk proteins upon export of the complex into the cytoplasm [78,82].…”