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Biomedical subjects

Elizabeth A Craig

Publications and source records attributed to Elizabeth A Craig.

26 records · Page 2Linked to original sources
PubMed2003

Ssq1, a mitochondrial Hsp70 involved in iron-sulfur (Fe/S) center biogenesis. Similarities to and differences from its bacterial counterpart.

The results of in vivo and in organellar experiments indicate that the Hsp70 Ssq1 and the J-protein Jac1 function together to assist in the biogenesis of iron-sulfur (Fe/S) centers in the mitochondrial matrix. Here we present biochemical evidence supporting this idea. Isu, the proposed scaffold on which Fe/S centers are assembled, is a substrate for both Jac1 and Ssq1. Jac1 and Isu1 cooperatively stimulate the ATPase activity of Ssq1. In addition, Jac1 facilitates the interaction of Ssq1 with Isu1 in the presence of ATP. These findings are consistent with the role in Fe/S biogenesis previously proposed for the bacterial Hsp70 Hsc66 and J-protein Hsc20 that interact with the bacterial Isu homologue IscU. However, unlike the bacterial Hsp70, we found that Ssq1 has a high affinity for nucleotide, and shares a nucleotide exchange factor, Mge1, with a second mitochondrial Hsp70, Ssc1. Thus, whereas the bacterial and mitochondrial chaperone systems share critical features, they possess significant biochemical differences as well.

Adenosine Triphosphatases↗
PubMed2003

Regulated cycling of mitochondrial Hsp70 at the protein import channel.

Hsp70 of the mitochondrial matrix (mtHsp70) provides a critical driving force for the import of proteins into mitochondria. Tim44, a peripheral inner-membrane protein, tethers it to the import channel. Here, regulated interactions were found to maximize occupancy of the active, adenosine 5'-triphosphate (ATP)-bound mtHsp70 at the channel through its intrinsic high affinity for Tim44, as well as through release of adenosine diphosphate (ADP)-bound mtHsp70 from Tim44 by the cofactor Mge1. A model peptide substrate rapidly released mtHsp70 from Tim44, even in the absence of ATP hydrolysis. In vivo, the analogous interaction of translocating polypeptide would release mtHsp70 from the channel. Consistent with the ratchet model of translocation, subsequent hydrolysis of ATP would trap the polypeptide, driving import by preventing its movement back toward the cytosol.

Adenosine Diphosphate↗
PubMed2003

Mental illness in women who have young children: current literature.

Postnatal depression is an illness that has been researched a great deal in recent years. While much is known about the prevalence and contributing factors, it is not clear whether antenatal interventions are successful in preventing postnatal depression. Mother-child relationships where the mother has a mental illness, have been reported to be more negative and may adversely affect the child's development. Many researchers discuss the importance of supporting such families, not only to improve their current situation, but also to help prevent the development of mental health problems in the children.

Adult↗
PubMed2003

Ribosome-tethered molecular chaperones: the first line of defense against protein misfolding?

Folding of many cellular proteins is facilitated by molecular chaperones. Analysis of both prokaryotic and lower eukaryotic model systems has revealed the presence of ribosome-associated molecular chaperones, thought to be the first line of defense against protein aggregation as translating polypeptides emerge from the ribosome. However, structurally unrelated chaperones have evolved to carry out these functions in different microbes. In the yeast Saccharomyces cerevisiae, an unusual complex of Hsp70 and J-type chaperones associates with ribosome-bound nascent chains, whereas in Escherichia coli the ribosome-associated peptidyl-prolyl-cis-trans isomerase, trigger factor, plays a predominant role.

Animals↗
PubMed2003

Specificity of class II Hsp40 Sis1 in maintenance of yeast prion [RNQ+].

Sis1 and Ydj1, functionally distinct heat shock protein (Hsp)40 molecular chaperones of the yeast cytosol, are homologs of Hdj1 and Hdj2 of mammalian cells, respectively. Sis1 is necessary for propagation of the Saccharomyces cerevisiae prion [RNQ(+)]; Ydj1 is not. The ability to function in [RNQ(+)] maintenance has been conserved, because Hdj1 can function to maintain Rnq1 in an aggregated form in place of Sis1, but Hdj2 cannot. An extended glycine-rich region of Sis1, composed of a region rich in phenylalanine residues (G/F) and another rich in methionine residues (G/M), is critical for prion maintenance. Single amino acid alterations in a short stretch of amino acids of the G/F region of Sis1 that are absent in the otherwise highly conserved G/F region of Ydj1 cause defects in prion maintenance. However, there is some functional redundancy within the glycine-rich regions of Sis1, because a deletion of the adjacent glycine/methionine (G/M) region was somewhat defective in propagation of [RNQ(+)] as well. These results are consistent with a model in which the glycine-rich regions of Hsp40s contain specific determinants of function manifested through interaction with Hsp70s.

Amino Acid Sequence↗
PubMed2002

Novel G-protein complex whose requirement is linked to the translational status of the cell.

G proteins, which bind and hydrolyze GTP, are involved in regulating a variety of critical cellular processes, including the process of protein synthesis. Many members of the subfamily of elongation factor class G proteins interact with the ribosome and function to regulate discrete steps during the process of protein synthesis. Despite sequence similarity to factors involved in translation, a role for the yeast Hbs1 protein has not been defined. In this work we have identified a genetic relationship between genes encoding components of the translational apparatus and HBS1. HBS1, while not essential for viability, is important for efficient growth and protein synthesis under conditions of limiting translation initiation. The identification of an Hbs1p-interacting factor, Dom34p, which shares a similar genetic relationship with components of the translational apparatus, suggests that Hbs1p and Dom34p may function as part of a complex that facilitates gene expression. Dom34p contains an RNA binding motif present in several ribosomal proteins and factors that regulate translation of specific mRNAs. Thus, Hbs1p and Dom34p may function together to help directly or indirectly facilitate the expression either of specific mRNAs or under certain cellular conditions.

Amino Acid Sequence↗
PubMedDate not supplied

Parenting programs for women with mental illness who have young children: a review.

OBJECTIVE: To provide an overview of the literature relevant to, and describing, parenting programs for women with mental illness who have young children. METHOD: A literature search was undertaken, including MEDLINE, PsycINFO, CINAHL, Cochrane Database of Systematic Reviews and EMBASE: Psychiatry. Searches were limited to English journals and books and to the last five years in the first instance, with earlier literature considered where appropriate. RESULTS: Maternal mental illness can impact negatively on a child's life, especially where an insecure attachment is formed between mother and baby during the important early developmental years. The potential sequelae of maternal mental illness for children include impaired cognitive development, behavioural difficulties and increased risk of psychiatric disorder. Effective parenting skills are suggested to be a protective factor against these sequelae. However, the effects of parenting programs for women with mental illness have not been empirically tested, so that the potential long-term benefits of such interventions are not known. CONCLUSIONS: Parenting skills training for women with mental illness may be a useful selective preventive intervention. It is unlikely generic programs will be suitable. Rather, interventions for women with a mental illness will need to address the commonly experienced parenting problems as well as the more specific needs of women with mental illness.

Adult↗