High impact information on RRD1

• To understand the molecular mechanism of PTPA activity, Ypa1 was cocrystallized with a proline-containing PPIase peptide substrate [1].
• Strains lacking both NCS1 and NOH1 were inviable and arrested as unbudded cells, implying that PTPA function is required for proper G(1) progression [2].
• The phosphotyrosyl phosphatase activator, Ncs1p (Rrd1p), functions with Cla4p to regulate the G(2)/M transition in Saccharomyces cerevisiae [2].
• Genetic and biochemical evidence suggested that the phosphatase Sit4p is a target for Ncs1p [2].
• The point mutant Asp205 --> Gly (in Ypa1) identified this amino acid as essential for both activities [3].

Biological context of RRD1

• The Saccharomyces cerevisiae phosphatase activator RRD1 is required to modulate gene expression in response to rapamycin exposure [4].
• Deletion of RRD1 caused pleiotropic phenotypes under a wide range of conditions, including sensitivity to Ca2+, vanadate, ketoconazole, cycloheximide and Calcofluor white, and resistance to caffeine and rapamycin [5].
• The Saccharomyces cerevisiae homologue YPA1 of the mammalian phosphotyrosyl phosphatase activator of protein phosphatase 2A controls progression through the G1 phase of the yeast cell cycle [6].
• A yeast homologue of the human phosphotyrosyl phosphatase activator PTPA is implicated in protection against oxidative DNA damage induced by the model carcinogen 4-nitroquinoline 1-oxide [7].
• Overexpression of NCS-1 has been shown to enhance evoked neurotransmitter release, paired-pulse facilitation and exocytosis in several neuronal and neuroendocrine cell types [8].

Anatomical context of RRD1

• A simple, improved procedure for the isolation of the phosphotyrosyl phosphatase activator (PTPA) from rabbit skeletal muscle has been developed [9].

Associations of RRD1 with chemical compounds

• The yeast phosphotyrosyl phosphatase activator protein, yPtpa1/Rrd1, interacts with Sit4 phosphatase to mediate resistance to 4-nitroquinoline-1-oxide and UVA [10].
• One of the mutants was defective in a gene designated yPTPA1, encoding a protein related to the human phosphotyrosyl phosphatase activator hPTPA, which is believed to play a role in activating the serine/threonine phosphatase PP2A [10].
• Recent experiments suggest that NCS-1 interacts directly with phosphatidylinositol 4-hydroxykinase in yeast as well as mammalian cells, suggesting that it may enhance neuronal secretion by modulating cellular trafficking steps in a phosphoinositide-dependent manner [8].

Regulatory relationships of RRD1

• Strikingly, the interaction of Ypa2 with yeast PP2A is promoted by the presence of Ypa1, suggesting a positive role of Ypa1 in the regulation of PP2A association with other interacting proteins [11].

Other interactions of RRD1

• While deletion of both YPA genes is lethal, deletion of YPA1 alone results in a phenotype resembling that of PP2A-deficient strains in specific aspects such as aberrant bud morphology, abnormal actin distribution, and similar growth defects under various growth conditions [12].

References