• Archives of Pharmacal Research
• /
• v.21 no.6
• /
• pp.629-633
• /
• 1998

In addition to selecting proteins for degradation by the 26S proteasome, ubiqitination appears to serve other regulatory functions, including for endosomal/lysosomal targeting, protein translocation, and enzyme modification. Currently, little is known how multiubiquitin chains are recognized by these cellular mechanisms. Within the 26S proteasome, one subunit (Mcb1/S5a) has been identified that has affinity for multiubiquitin chains and may function as a ubiquitin receptor. We recently found that a non-proteasomal protein p62 also preferentially binds multiubiquitin chains and forms a novel cytoplasmic structure "sequestosome" which serves as a storage place for ubiquitinated proteins. In the present manuscript, the role and regulation of p62 in relation to the sequestosomal function will be reviewed.

• Archives of Pharmacal Research
• /
• v.25 no.6
• /
• pp.759-769
• /
• 2002

Mutated forms of ras are found in many human tumors and the rate of incidence is significantly higher in colon and pancreatic cancers. The protein product from the ras oncogene is a small G-protein, $p21^{ras}{\;}(Ras)$ that is known to playa key role in the signal transduction cascade and cell differentiation and proliferation. Mutated Ras is unable to regulate itself and remains constantly activated, leading to uncontrolled cell growth. The function of Ras in signal transduction requires its location near the growth factor receptor at the cell membrane. However, Ras does not have a transmembrane domain. Ras requires farnesylation to increase its hydrophobicity and subsequent plasma membrane association for its transforming activity. This key post-translational modification is catalyzed by the enzyme Ras farnesyltransferase (FTase), which transfers a farnesyl group from farnesylpyrophosphate to the C-terminal cysteine of the Ras protein. The requirement has focused attention on FTase as a target for therapeutic intervention. Selective inhibition of FTase will prevent Ras protein from association with the plasma membrane, leading to a disruption of oncogenic Ras function.

• BMB Reports
• /
• v.34 no.2
• /
• pp.95-101
• /
• 2001

Tissue transglutaminase (TGII, $G{\alpha}h$) belongs to a family of enzymes which catalyze post-translational modification of proteins by forming isopeptides via $Ca^{2+}$-dependent reaction. Although TGII-mediated formation of isopeptides has been implicated to play a role in a variety of cellular processes, the physiological function of TGII remains unclear. In addition to this Tease activity, TGII is a guanosine triphosphatase (GTPase) which binds and hydrolyzes GTP It is now well recognized that the GTPase action of TGII regulates a receptor-mediated transmembrane signaling, functioning as a signal transducer of the receptor. This TGII function signifies that TGII is a new class of GTP-binding regulatory protein (G-protein) that differs from "Classical" heterotrimeric G-proteins. Regulation of enzyme is an important biological process for maintaining cell integrity. This review summarizes the recent development in regulation of TGII that may help for the better understanding of this unique enzyme. Since activation and inactivation of GTPase of TGII are similar to the heterotrimeric G-proteins, the regulation of heterotrimeric G-protein in the transmembrane signaling is also discussed.

• Journal of Oral Medicine and Pain
• /
• v.20 no.1
• /
• pp.7-18
• /
• 1995

The Purpose of this article is to describe the biochemical properties and biological functions of several salivary proteins that possess the unusual properties of inhibiting spontaneous and secondary precipitation of calcium phosphate. This function is very important since human salivary secretion is supersaturated with respect to calcium phosphate. Biological function of statherin, proline rich protein (PRP) and histidine rich protein (HRP) is to inhibit precipitation of calcium phosphate in salivary glands, in the oral fluids, and onto tooth surfaces. The resulting supersaturated state of the salivary secretions contributes a protective and reparative environment which is important for the integrity of the tooth. Beneficial consequences of salivary supersaturation with respect to calcium phosphate are selectively expressed in the oral cavity- that is, protection is provided for the dental enamel-while undesirable consequences, for example, precipitation of calcium phosphates in the salivary glands and onto the teeth do not occur. Purification and structural characteristics of these proteins as well as clinical significance of functions of each protein will be discussed.

• BMB Reports
• /
• v.43 no.12
• /
• pp.795-800
• /
• 2010

Huntingtin-interacting protein 1-related (HIP1r) is known to function in clathrin-mediated endocytosis and regulation of the actin cytoskeleton, which occurs continuously in non-dividing cells. This study reports a new function for HIP1r in mitosis. Green fluorescent protein-fused HIP1r localizes to the mitotic spindles. Depletion of HIP1r by RNA interference induces misalignment of chromosomes and prolonged mitosis, which is associated with decreased proliferation of HIP1r-deficeint cells. Chromosome misalignment leads to missegregation and ultimately production of multinucleated cells. Depletion of HIP1r causes persistent activation of the spindle checkpoint in misaligned chromosomes. These findings suggest that HIP1r plays an important role in regulating the attachment of spindle microtubules to chromosomes during mitosis, an event that is required for accurate congression and segregation of chromosomes. This finding may provide new insights that improve the understanding of various human diseases involving HIP1r as well as its fusion genes.

• Development and Reproduction
• /
• v.26 no.3
• /
• pp.117-126
• /
• 2022

Bromodomain-containing protein 7 (BRD7) participates in many cellular processes and embryo development. BRD7 is down-regulated in various cancers and evidence of its tumor suppressor function has been accumulating. Here, we identified transforming stimulated clone 22 (TSC-22) as a novel BRD7 interacting protein and show its novel function as a positive regulator of BRD7. We found that TSC-22 expression potentiated the inactivation of the extracellular signal-regulate kinase (ERK) pathway by BRD7. Our data establishes TSC-22 as a modulator of BRD7 and unravels the molecular mechanisms that drive the synergistic tumor-suppressing effects of TSC-22 and BRD7. Our findings may open new avenues for developing novel molecular therapies for tumors exhibiting down-regulated BRD7 and/or TSC-22.

• 한국생물공학회:학술대회논문집
• /
• 2005.04a
• /
• pp.295-295
• /
• 2005

• Journal of Korean Society of Forest Science
• /
• v.99 no.4
• /
• pp.501-507
• /
• 2010

Formaldehyde responsive protein(FRP) 1 belongs to the family of universal stress protein(USP) and is known to respond to stress caused by fumigation of gaseous volatile organic compounds(VOCs) such as formaldehyde and toluene. However, the molecular function of this protein is not well understood at cellular and molecular level. In this study, loss of function mutant of FRP1 generated by T-DNA insertion(frp1-4) has been isolated from Arabidopsis thaliana and the function of FRP1 was characterized. The loss-of-function mutant of FRP1 appeared slight growth defects with shorter stem and rosette leaves compared to wild type. In addition, the damage caused by exogenous VOCs was more severe in frp1-4 than in control. Therefore, Arabidopsis FRP1 seems to be the protein involved not only in the growth and development of plant but also the stress resistance against toxic volatile organic compounds.

• BMB Reports
• /
• v.39 no.4
• /
• pp.355-360
• /
• 2006

To gain a better understanding on the function of the potato Solanum tuberosum Multiprotein Bridging Factor 1 protein (StMBF1) its interaction with the TATA box binding protein (TBP) was demonstrated. In addition we reported that StMBF1 rescues the yeast mbf1 mutant phenotype, indicating its role as a plant co-activator. These data reinforce the hypothesis that MBF1 function is also conserved among non closely related plant species. In addition, measurement of StMBF1 protein level by Western blot using anti-StMBF1 antibodies indicated that the protein level increased upon $H_2O_2$ and heat shock treatments. However, the potato $\beta$-1,3-glucanase protein level was not changed under the same experimental conditions. These data indicate that StMBF1 participates in the cell stress response against oxidative stress allowing us to suggest that MBF1 genes from different plant groups may share similar functions.

• BMB Reports
• /
• v.38 no.5
• /
• pp.550-554
• /
• 2005

YKR049C is a mitochondrial protein in Saccharomyces cerevisiae that is conserved among yeast species, including Candida albicans. However, no biological function for YKR049C has been ascribed based on its primary sequence information. In the present study, NMR spectroscopy was used to determine the putative biological function of YKR049C based on its solution structure. YKR049C shows a well-defined thioredoxin fold with a unique insertion of helices between two $\beta$-strands. The central $\beta$-sheet divides the protein into two parts; a unique face and a conserved face. The 'unique face' is located between ${\beta}2$ and ${\beta}3$. Interestingly, the sequences most conserved among YKR049C families are found on this 'unique face', which incorporates L109 to E114. The side chains of these conserved residues interact with residues on the helical region with a stretch of hydrophobic surface. A putative active site composed by two short helices and a single Cys97 was also well observed. Our findings suggest that YKR049C is a redox protein with a thioredoxin fold containing a single active cysteine.