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Amy Chang

Publications and source records attributed to Amy Chang.

12 recordsLinked to original sources
PubMed2025

Psychological and emotional impacts of communicating breast cancer risk using multifactorial assessment with polygenic risk score: Findings from PERSPECTIVE I&I.

PURPOSE: To examine the psychological and emotional outcomes of personalized breast cancer risk communication up to 1 year after disclosure in a risk-stratified breast screening preimplementation study (Personalized Risk Assessment for Prevention and Early Detection of Breast Cancer: Integration and Implementation). METHODS: Among 3753 females aged 40 to 69, unaffected by breast cancer, with a prior mammogram, and who underwent multifactorial risk assessment to estimate their 10-year breast cancer risk, 2734 completed follow-up questionnaires up to 1 year after risk communication: 78.5% were at average risk, 16.5% at higher than average risk, and 5.0% at high risk. The impact of risk communication on breast cancer worry and psychological distress and factors associated with decisional regret were examined. RESULTS: Breast cancer worry and psychological distress scores remained low after risk communication and at 1 year follow-up. Up to 1 year after disclosure, small significant differences in breast cancer worry were observed between risk levels. Decisional regret was very low 1 year after risk communication. Lower levels of decisional regret were significantly associated with some factors, including higher satisfaction with the information received. CONCLUSION: This study suggests that personalized breast cancer risk communication has low negative psychological and emotional effects and highlights the importance of the information received for implementing this approach at population level.

Humans↗
PubMed2006

Multiple degradation pathways for misfolded mutants of the yeast plasma membrane ATPase, Pma1.

To understand protein sorting and quality control in the secretory pathway, we have analyzed intracellular trafficking of the yeast plasma membrane ATPase, Pma1. Pma1 is ideal for such studies because it is a very abundant polytopic membrane protein, and its localization and activity at the plasma membrane are essential for cell viability and growth. We have tested whether the cytoplasmic amino- and carboxyl-terminal domains of Pma1 carry sorting information. As the sole copy of Pma1, mutants truncated at either NH2 or COOH termini are targeted at least partially to the plasma membrane and have catalytic activity to sustain cell viability. The mutants are also delivered to degradative pathways. Strikingly, NH2- and COOH-terminal Pma1 mutants are differentially recognized for degradation at distinct cellular locales. COOH-terminal mutants are recognized for destruction by endoplasmic reticulum-associated degradation. By contrast, NH2-terminal mutants escape detection by endoplasmic reticulum-associated degradation entirely, and undergo endocytosis for vacuolar degradation after apparently normal cell surface targeting. Both NH2- and COOH-terminal mutants are conformationally abnormal, as revealed by increased sensitivity to tryptic cleavage, but are able to assemble to form oligomers. We propose that different quality control mechanisms may assess discrete domains of Pma1 rather than a global conformational state.

Catalytic Domain↗
PubMed2006

Quality control of a mutant plasma membrane ATPase: ubiquitylation prevents cell-surface stability.

The plasma membrane ATPase, Pma1, has remarkable longevity at the cell surface. In contrast to the wild-type protein, the temperature-sensitive mutant Pma1-10 is misfolded and undergoes rapid removal from the cell surface for vacuolar degradation. At the restrictive temperature, Pma1-10 becomes ubiquitylated before or upon arrival at the plasma membrane. Internalization from the plasma membrane and vacuolar degradation of Pma1-10 is dependent on the ubiquitin-interacting motif (UIM) of the epsin Ent1, suggesting recognition of ubiquitylated substrate by the endocytic machinery. Surprisingly, ubiquitylation of Pma1-10 is reversed when its internalization is blocked in an end3 mutant. Under these conditions, Pma1-10 acquires association with detergent-insoluble, glycolipid-enriched complexes (DIGs) which has been suggested to promote stability of wild-type Pma1. Ubiquitylation does not cause DIG exclusion because a Pma1-Ub fusion protein is not significantly excluded from DIGs. We suggest that ubiquitylation of Pma1-10 represents a component of a quality control mechanism that targets the misfolded protein for removal from the plasma membrane. Rapid internalization of Pma1-10 caused by its ubiquitylation may preempt establishment of stabilizing interactions.

Carrier Proteins↗
PubMed2004

Ubiquitin-mediated targeting of a mutant plasma membrane ATPase, Pma1-7, to the endosomal/vacuolar system in yeast.

Pma1-7 is a mutant plasma membrane ATPase that is impaired in targeting to the cell surface at 37 degrees C and is delivered instead to the endosomal/vacuolar pathway for degradation. We have proposed that Pma1-7 is a substrate for a Golgibased quality control mechanism. By contrast with wild-type Pma1, Pma1-7 is ubiquitinated. Ubiquitination and endosomal targeting of Pma1-7 is dependent on the Rsp5-Bul1-Bul2 ubiquitin ligase protein complex but not the transmembrane ubiquitin ligase Tul1. Analysis of Pma1-7 ubiquitination in mutants blocked in protein transport at various steps of the secretory pathway suggests that ubiquitination occurs after ER exit but before endosomal entry. In the absence of ubiquitination in rsp5-1 cells, Pma1-7 is delivered to the cell surface and remains stable. Nevertheless, Pma1-7 remains impaired in association with detergent-insoluble glycolipid-enriched complexes in rsp5-1 cells, suggesting that ubiquitination is not the cause of Pma1-7 exclusion from rafts. In vps1 cells in which protein transport into the endosomal pathway is blocked, Pma1-7 is routed to the cell surface. On arrival at the plasma membrane in vps1 cells, Pma1-7 remains stable and its ubiquitination disappears, suggesting deubiquitination activity at the cell surface. We suggest that Pma1-7 sorting and fate are regulated by ubiquitination.

Adaptor Proteins, Signal Transducing↗
PubMed2003

Substrate recognition in ER-associated degradation mediated by Eps1, a member of the protein disulfide isomerase family.

Pma1-D378N is a misfolded plasma membrane protein in yeast that is prevented from delivery to the cell surface and targeted instead for ER-associated degradation (ERAD). Degradation of Pma1-D378N is dependent on the ubiquitin ligase Doa10 and the ubiquitin chaperone Cdc48. Recognition of Pma1-D378N by the ERAD pathway is dependent on Eps1, a transmembrane member of the protein disulfide isomerase (PDI) oxidoreductase family. Eps1 has two thioredoxin-like domains containing a CPHC and a CDKC active site. Although Eps1 interaction with wild-type Pma1 was not detected, Eps1 co-immunoprecipitates with Pma1-D378N. Eps1 interaction with Pma1-D378N requires the CPHC motif, although both thioredoxin-like domains appear to cooperate in substrate recognition. In the absence of the native transmembrane domain and cytoplasmic tail of Eps1, degradation of Pma1-D378N is slowed, suggesting that Eps1 facilitates presentation of substrate to membrane-bound components of the degradation machinery. Genetic interactions with other mutants of the ERAD machinery and induction of the unfolded protein response in eps1Delta cells support a general role for Eps1 as a recognition component of the ERAD pathway.

Base Sequence↗
PubMed2003

Lecture versus Web tutorial for pharmacy students' learning of MDI technique.

OBJECTIVE: To compare pharmacy students' acquired knowledge and ability to assess metered-dose inhaler (MDI) technique after a traditional lecture versus a Web-based MDI technique tutorial. METHODS: All 42 third-year PharmD students completed a baseline MDI technique knowledge test and were then randomized into 1 of 3 groups. The Web group completed the tutorial on the college dispensing laboratory computers; the lecture group participated in the MDI technique excerpt of the asthma therapeutics lecture; and the control group participated in a 15-minute discussion of participants' hobbies. Afterward, participants in each group completed an identical MDI technique knowledge posttest. Students then observed a standardized mock patient perform MDI technique, documenting steps that were conducted incorrectly. MDI technique knowledge test and MDI technique evaluation test scores were compared between groups using repeated measures ANOVA. RESULTS: There was no significant difference in the baseline MDI technique knowledge test scores between groups. The post-MDI technique knowledge test scores for the Web and lecture groups did not differ significantly (p = 0.38), and both were significantly different from the control group (p < 0.001). MDI technique knowledge scores increased significantly for the Web and lecture groups from pre- to post-assessment, but did not change for the control group. A 2-way repeated measures ANOVA analysis demonstrated no significant interaction of subject and group characteristics. The MDI technique evaluation scores for the Web and lecture groups were not significantly different (p = 0.50), and both were significantly different from the control group (p </= 0.001). CONCLUSIONS: The Web-based MDI technique tutorial was as effective as the standard lecture format in pharmacy students acquiring knowledge of MDI technique and in evaluating a mock-patient exhibiting incorrect MDI technique. Further testing is required to assess the longitudinal effect of the program.

Curriculum↗
PubMed2002

Sphingoid base synthesis is required for oligomerization and cell surface stability of the yeast plasma membrane ATPase, Pma1.

The plasma membrane H(+)-ATPase, Pma1, is an essential and long-lived integral membrane protein. Previous work has demonstrated that the Pma1-D378N mutant is a substrate for endoplasmic reticulum (ER)-associated degradation and causes a dominant negative effect on cell growth by preventing ER export of wild-type Pma1. We now show that Pma1-D378N is ubiquitylated, and it heterooligomerizes with wild-type Pma1, resulting in ubiquitylation and ER-associated degradation of wild-type Pma1. In temperature-sensitive lcb1-100 cells, defective in sphingoid base synthesis, Pma1 fails to oligomerize. At 30 degrees C, lcb1-100 is a suppressor of pma1-D378N because wild-type Pma1 fails to heterooligomerize with Pma1-D378N; wild-type Pma1 moves to the cell surface, indicating that oligomerization is not required for delivery to the plasma membrane. Even in the absence of Pma1-D378N, wild-type Pma1 is ubiquitylated and it undergoes internalization from the cell surface and vacuolar degradation at 30 degrees C in lcb1-100 cells. At 37 degrees C in lcb1-100 cells, a more severe defect occurs in sphingoid base synthesis, and targeting of newly synthesized Pma1 to the plasma membrane is impaired. These data indicate requirements for sphingolipids at three discrete stages: Pma1 oligomerization at the ER, targeting to the plasma membrane, and stability at the cell surface.

Blotting, Western↗
PubMed2002

An ER membrane protein, Sop4, facilitates ER export of the yeast plasma membrane [H+]ATPase, Pma1.

We have analyzed the mechanism by which Sop4, a novel ER membrane protein, regulates quality control and intracellular transport of Pma1-7, a mutant plasma membrane ATPase. At the restrictive temperature, newly synthesized Pma1-7 is targeted for vacuolar degradation instead of being correctly delivered to the cell surface. Loss of Sop4 at least partially corrects vacuolar mislocalization, allowing Pma1-7 routing to the plasma membrane. Ste2-3 is a mutant pheromone receptor which, like Pma1-7, is defective in targeting to the cell surface, resulting in a mating defect. sop4delta suppresses the mating defect of ste2-3 cells as well as the growth defect of pma1-7. Visualization of newly synthesized Pma1-7 in sop4delta cells by indirect immunofluorescence reveals delayed export from the ER. Similarly, ER export of wild-type Pma1 is delayed in the absence of Sop4 although intracellular transport of Gas1 and CPY is unaffected. These observations suggest a model in which a selective increase in ER residence time for Pma1-7 may allow it to achieve a more favorable conformation for subsequent delivery to the plasma membrane. In support of this model, newly synthesized Pma1-7 is also routed to the plasma membrane upon release from a general block of ER-to-Golgi transport in sec13-1 cells.

Base Sequence↗
PubMed2002

Secretory pathway quality control operating in Golgi, plasmalemmal, and endosomal systems.

Exportable proteins that have significant defects in nascent polypeptide folding or subunit assembly are frequently retained in the endoplasmic reticulum and subject to endoplasmic reticulum-associated degradation by the ubiquitin-proteasome system. In addition to this, however, there is growing evidence for post-endoplasmic reticulum quality control mechanisms in which mutant or non-native exportable proteins may undergo anterograde transport to the Golgi complex and post-Golgi compartments before intracellular disposal. In some instances, these proteins may undergo retrograde transport back to the endoplasmic reticulum with re-targeting to the endoplasmic reticulum-associated degradation pathway; in other typical cases, they are targeted into the endosomal system for degradation by vacuolar/lysosomal proteases. Such quality control targeting is likely to involve recognition of features more commonly expressed in mutant proteins, but may also be expressed by wild-type proteins, especially in cells with perturbation of local environments that are essential for normal protein trafficking and stability in the secretory pathway and at the cell surface.

Animals↗