Susan Michaelis

Endoplasmic reticulum membrane localization of Rce1p and Ste24p, yeast proteases involved in carboxyl-terminal CAAX protein processing and amino-terminal a-factor cleavage

Schmidt, Walter K., Tam, Amy, Fujimura-Kamada, Konomi, Michaelis, Susan

Proteins terminating in the CAAX motif, for example Ras and the yeast a-factor mating pheromone, are prenylated, trimmed of their last three amino acids, and carboxyl-methylated. The enzymes that...

The Saccharomyces cerevisiae Prenylcysteine Carboxyl Methyltransferase Ste14p Is in the Endoplasmic Reticulum Membrane

Romano, Julia D., Schmidt, Walter K., Michaelis, Susan

Eukaryotic proteins containing a C-terminal CAAX motif undergo a series of posttranslational CAAX-processing events that include isoprenylation, C-terminal proteolytic cleavage, and carboxyl...

Ste6p Mutants Defective in Exit from the Endoplasmic Reticulum (ER) Reveal Aspects of an ER Quality Control Pathway in Saccharomyces cerevisiae

Loayza, Diego, Tam, Amy, Schmidt, Walter K., Michaelis, Susan

We are studying the intracellular trafficking of the multispanning membrane protein Ste6p, the a-factor transporter in Saccharomyces cerevisiae and a member of the ATP-binding cassette superfamily of...

Hsp70 Molecular Chaperone Facilitates Endoplasmic Reticulum-associated Protein Degradation of Cystic Fibrosis Transmembrane Conductance Regulator in Yeast

Zhang, Yimao, Nijbroek, Gaby, Sullivan, Mara L., McCracken, Ardythe A., Watkins, Simon C., Michaelis, Susan, ...

Membrane and secretory proteins fold in the endoplasmic reticulum (ER), and misfolded proteins may be retained and targeted for ER-associated protein degradation (ERAD). To elucidate the mechanism by...

Topological and Mutational Analysis of Saccharomyces cerevisiae Ste14p, Founding Member of the Isoprenylcysteine Carboxyl Methyltransferase Family

Romano, Julia D., Michaelis, Susan

Eukaryotic proteins that terminate in a CaaX motif undergo three processing events: isoprenylation, C-terminal proteolytic cleavage, and carboxyl methylation. In Saccharomyces cerevisiae, the latter...

Role for the Ubiquitin-Proteasome System in the Vacuolar Degradation of Ste6p, the a-Factor Transporter in Saccharomyces cerevisiae

Loayza, Diego, Michaelis, Susan

Ste6p, the a-factor transporter in Saccharomyces cerevisiae, is a multispanning membrane protein with 12 transmembrane spans and two cytosolic ATP binding domains. Ste6p belongs to the ATP binding...

Localization, Regulation, and Substrate Transport Properties of Bpt1p, a Saccharomyces cerevisiae MRP-Type ABC Transporter

Sharma, Kailash Gulshan, Mason, Deborah L., Liu, Guosheng, Rea, Philip A., Bachhawat, Anand K., Michaelis, Susan

Saccharomyces cerevisiae Bpt1p is an ATP-binding cassette (ABC) protein that belongs to the MRP subfamily and is a close homologue of the glutathione conjugate (GS conjugate) transporter Ycf1p. The...

Zmpste24 deficiency in mice causes spontaneous bone fractures, muscle weakness, and a prelamin A processing defect

Bergo, Martin O., Gavino, Bryant, Ross, Jed, Schmidt, Walter K., Hong, Christine, Kendall, Lonnie V., ...

Zmpste24 is an integral membrane metalloproteinase of the endoplasmic reticulum. Biochemical studies of tissues from Zmpste24-deficient mice (Zmpste24−/−) have indicated a role for Zmpste24 in...

Requirement of the N-Terminal Extension for Vacuolar Trafficking and Transport Activity of Yeast Ycf1p, an ATP-binding Cassette Transporter

Mason, Deborah L., Michaelis, Susan

Ycf1p is the prototypical member of the yeast multidrug resistance-associated protein (MRP) subfamily of ATP-binding cassette (ABC) transporters. Ycf1p resides in the vacuolar membrane and mediates...

A Region within a Lumenal Loop of Saccharomyces cerevisiae Ycf1p Directs Proteolytic Processing and Substrate Specificity

Mason, Deborah L., Mallampalli, Monica P., Huyer, Gregory, Michaelis, Susan

Ycf1p, a member of the yeast multidrug resistance-associated protein (MRP) subfamily of ATP-binding cassette proteins, is a vacuolar membrane transporter that confers resistance to a variety of toxic...

A Striking Quality Control Subcompartment in Saccharomyces cerevisiae: The Endoplasmic Reticulum-associated Compartment

Huyer, Gregory, Longsworth, Gaby L., Mason, Deborah L., Mallampalli, Monica P., McCaffery, J. Michael, Wright, Robin L., ...

The folding of nascent secretory and membrane proteins is monitored by the endoplasmic reticulum (ER) quality control system. Misfolded proteins are retained in the ER and can be removed by...

Prelamin A endoproteolytic processing in vitro by recombinant Zmpste24

Corrigan, Douglas P., Kuszczak, Danuta, Rusinol, Antonio E., Thewke, Douglas P., Hrycyna, Christine A., Michaelis, Susan, ...

The nuclear lamins form a karyoskeleton providing structural rigidity to the nucleus. One member of the lamin family, lamin A, is first synthesized as a 74 kDa precursor, prelamin A. After the...

Inhibiting farnesylation reverses the nuclear morphology defect in a HeLa cell model for Hutchinson-Gilford progeria syndrome

Mallampalli, Monica P., Huyer, Gregory, Bendale, Pravin, Gelb, Michael H., Michaelis, Susan

Hutchinson-Gilford progeria syndrome (HGPS) is a devastating premature aging disease resulting from a mutation in the LMNA gene, which encodes nuclear lamins A and C. Lamin A is synthesized as a...

Endoplasmic reticulum membrane localization of Rce1p and Ste24p, yeast proteases involved in carboxyl-terminal CAAX protein processing and amino-terminal a-factor cleavage

Schmidt, Walter K., Tam, Amy, Fujimura-Kamada, Konomi, Michaelis, Susan

Proteins terminating in the CAAX motif, for example Ras and the yeast a-factor mating pheromone, are prenylated, trimmed of their last three amino acids, and carboxyl-methylated. The enzymes that...

The Saccharomyces cerevisiae Prenylcysteine Carboxyl Methyltransferase Ste14p Is in the Endoplasmic Reticulum Membrane

Romano, Julia D., Schmidt, Walter K., Michaelis, Susan

Eukaryotic proteins containing a C-terminal CAAX motif undergo a series of posttranslational CAAX-processing events that include isoprenylation, C-terminal proteolytic cleavage, and carboxyl...

Ste6p Mutants Defective in Exit from the Endoplasmic Reticulum (ER) Reveal Aspects of an ER Quality Control Pathway in Saccharomyces cerevisiae

Loayza, Diego, Tam, Amy, Schmidt, Walter K., Michaelis, Susan

We are studying the intracellular trafficking of the multispanning membrane protein Ste6p, the a-factor transporter in Saccharomyces cerevisiae and a member of the ATP-binding cassette superfamily of...

Hsp70 Molecular Chaperone Facilitates Endoplasmic Reticulum-associated Protein Degradation of Cystic Fibrosis Transmembrane Conductance Regulator in Yeast

Zhang, Yimao, Nijbroek, Gaby, Sullivan, Mara L., McCracken, Ardythe A., Watkins, Simon C., Michaelis, Susan, ...

Membrane and secretory proteins fold in the endoplasmic reticulum (ER), and misfolded proteins may be retained and targeted for ER-associated protein degradation (ERAD). To elucidate the mechanism by...

Topological and Mutational Analysis of Saccharomyces cerevisiae Ste14p, Founding Member of the Isoprenylcysteine Carboxyl Methyltransferase Family

Romano, Julia D., Michaelis, Susan

Eukaryotic proteins that terminate in a CaaX motif undergo three processing events: isoprenylation, C-terminal proteolytic cleavage, and carboxyl methylation. In Saccharomyces cerevisiae, the latter...

Role for the Ubiquitin-Proteasome System in the Vacuolar Degradation of Ste6p, the a-Factor Transporter in Saccharomyces cerevisiae

Loayza, Diego, Michaelis, Susan

Ste6p, the a-factor transporter in Saccharomyces cerevisiae, is a multispanning membrane protein with 12 transmembrane spans and two cytosolic ATP binding domains. Ste6p belongs to the ATP binding...

Localization, Regulation, and Substrate Transport Properties of Bpt1p, a Saccharomyces cerevisiae MRP-Type ABC Transporter

Sharma, Kailash Gulshan, Mason, Deborah L., Liu, Guosheng, Rea, Philip A., Bachhawat, Anand K., Michaelis, Susan

Saccharomyces cerevisiae Bpt1p is an ATP-binding cassette (ABC) protein that belongs to the MRP subfamily and is a close homologue of the glutathione conjugate (GS conjugate) transporter Ycf1p. The...

Zmpste24 deficiency in mice causes spontaneous bone fractures, muscle weakness, and a prelamin A processing defect

Bergo, Martin O., Gavino, Bryant, Ross, Jed, Schmidt, Walter K., Hong, Christine, Kendall, Lonnie V., ...

Zmpste24 is an integral membrane metalloproteinase of the endoplasmic reticulum. Biochemical studies of tissues from Zmpste24-deficient mice (Zmpste24−/−) have indicated a role for Zmpste24 in...

Requirement of the N-Terminal Extension for Vacuolar Trafficking and Transport Activity of Yeast Ycf1p, an ATP-binding Cassette Transporter

Mason, Deborah L., Michaelis, Susan

Ycf1p is the prototypical member of the yeast multidrug resistance-associated protein (MRP) subfamily of ATP-binding cassette (ABC) transporters. Ycf1p resides in the vacuolar membrane and mediates...

A Region within a Lumenal Loop of Saccharomyces cerevisiae Ycf1p Directs Proteolytic Processing and Substrate Specificity

Mason, Deborah L., Mallampalli, Monica P., Huyer, Gregory, Michaelis, Susan

Ycf1p, a member of the yeast multidrug resistance-associated protein (MRP) subfamily of ATP-binding cassette proteins, is a vacuolar membrane transporter that confers resistance to a variety of toxic...

A Striking Quality Control Subcompartment in Saccharomyces cerevisiae: The Endoplasmic Reticulum-associated Compartment

Huyer, Gregory, Longsworth, Gaby L., Mason, Deborah L., Mallampalli, Monica P., McCaffery, J. Michael, Wright, Robin L., ...

The folding of nascent secretory and membrane proteins is monitored by the endoplasmic reticulum (ER) quality control system. Misfolded proteins are retained in the ER and can be removed by...

Prelamin A endoproteolytic processing in vitro by recombinant Zmpste24

Corrigan, Douglas P., Kuszczak, Danuta, Rusinol, Antonio E., Thewke, Douglas P., Hrycyna, Christine A., Michaelis, Susan, ...

The nuclear lamins form a karyoskeleton providing structural rigidity to the nucleus. One member of the lamin family, lamin A, is first synthesized as a 74 kDa precursor, prelamin A. After the...

Inhibiting farnesylation reverses the nuclear morphology defect in a HeLa cell model for Hutchinson-Gilford progeria syndrome

Mallampalli, Monica P., Huyer, Gregory, Bendale, Pravin, Gelb, Michael H., Michaelis, Susan

Hutchinson-Gilford progeria syndrome (HGPS) is a devastating premature aging disease resulting from a mutation in the LMNA gene, which encodes nuclear lamins A and C. Lamin A is synthesized as a...

Saccharomyces cerevisiae a-Factor Mutants Reveal Residues Critical for Processing, Activity, and Export

Huyer, Gregory, Kistler, Amy, Nouvet, Franklin J., George, Carolyn M., Boyle, Meredith L., Michaelis, Susan

The Saccharomyces cerevisiae mating pheromone a-factor provides a paradigm for understanding the biogenesis of prenylated fungal pheromones. The biogenesis of a-factor involves multiple steps: (i)...

Biogenesis of the Saccharomyces cerevisiae Mating Pheromone a-Factor

Chen, Peng, Sapperstein, Stephanie K., Choi, Jonathan D., Michaelis, Susan

The Saccharomyces cerevisiae mating pheromone a-factor is a prenylated and carboxyl methylated extracellular peptide signaling molecule. Biogenesis of the a-factor precursor proceeds via a...

A Novel Membrane-associated Metalloprotease, Ste24p, Is Required for the First Step of NH2-terminal Processing of the Yeast a-Factor Precursor

Fujimura-Kamada, Konomi, Nouvet, Franklin J., Michaelis, Susan

Many secreted bioactive signaling molecules, including the yeast mating pheromones a-factor and α-factor, are initially synthesized as precursors requiring multiple intracellular processing enzymes...

Dual Roles for Ste24p in Yeast a-Factor Maturation: NH2-terminal Proteolysis and COOH-terminal CAAX Processing

Tam, Amy, Nouvet, Franklin J., Fujimura-Kamada, Konomi, Slunt, Hilda, Sisodia, Sangram S., Michaelis, Susan

Maturation of the Saccharomyces cerevisiae a-factor precursor involves COOH-terminal CAAX processing (prenylation, AAX tripeptide proteolysis, and carboxyl methylation) followed by cleavage of an...

Analysis of Prelamin A Biogenesis Reveals the Nucleus to be a CaaX Processing Compartment

Barrowman, Jemima, Hamblet, Corinne, George, Carolyn M., Michaelis, Susan

Proteins establish and maintain a distinct intracellular localization by means of targeting, retention, and retrieval signals, ensuring most proteins reside predominantly in one cellular location....

Analysis of Quality Control Substrates in Distinct Cellular Compartments Reveals a Unique Role for Rpn4p in Tolerating Misfolded Membrane Proteins

Metzger, Meredith Boyle, Michaelis, Susan

ER quality control (ERQC) prevents the exit of misfolded secretory and membrane proteins from the ER. A critical aspect of ERQC is a transcriptional response called the unfolded protein response...

Negative Regulation of the Yeast ABC Transporter Ycf1p by Phosphorylation within Its N-terminal Extension*

Paumi, Christian M., Chuk, Matthew, Chevelev, Igor, Stagljar, Igor, Michaelis, Susan

The yeast vacuolar membrane protein Ycf1p and its mammalian counterpart, MRP1, belong to the ABCC subfamily of ATP-binding cassette (ABC) transporters that rid cells of toxic endogenous and...

Degradation of a Cytosolic Protein Requires Endoplasmic Reticulum-associated Degradation Machinery*

Metzger, Meredith Boyle, Maurer, Matthew J., Dancy, Beverley M., Michaelis, Susan

Protein misfolding is monitored by a variety of cellular “quality control” systems. Endoplasmic reticulum (ER) quality control handles misfolded secretory and membrane proteins and is well...