Jaegyun Shin

p62 is a novel cellular protein which was initially identified as a phosphotyrosine-independent ligand of the SH2 domain of p56(lck). In the yeast two-hybrid system, p62 specifically interacted with ubiquitin in vivo. Furthermore, p62 bound to ubiquitin-conjugated Sepharose beads in vitro and was efficiently competed by soluble ubiquitin. The interaction was independent of ATP hydrolysis, and its dissociation did not require a reducing agent. Thus, p62 binds to ubiquitin noncovalently. Further a

Proper regulation of mitophagy for mitochondrial homeostasis is important in various inflammatory diseases. However, the precise mechanisms by which mitophagy is activated to regulate inflammatory responses remain largely unknown. The NLRP3 (NLR family, pyrin domain containing 3) inflammasome serves as a platform that triggers the activation of CASP1 (caspase 1) and secretion of proinflammatory cytokines. Here, we demonstrate that SESN2 (sestrin 2), known as stress-inducible protein, suppresses

Nuclear hormone receptors (NRs) are transcription factors whose activity is regulated by ligands and by coactivators or corepressors. We report the characterization of a new NR coregulator: proline-, glutamic acid-, leucine-rich protein 1 (PELP1), a novel human protein that comprises 1,282 amino acids and is localized on chromosome 17. The primary structure of PELP1 consists of several motifs present in most transcriptional regulators including nine NR-interacting boxes (LXXLL motifs), a zinc fi

The capsid protein of the West Nile virus (WNV) functions as an apoptotic agonist via the induction of mitochondrial dysfunction and the activation of caspases-9 and -3. Here, we have determined that the WNV capsid (WNVCp) is capable of binding to and sequestering HDM2 into the nucleolus. WNVCp was shown to interfere with the formation of the HDM2 and p53 complex, thereby causing the stabilization of p53 and the subsequent induction of its target apoptotic protein, Bax. Whereas WNVCp was capable

After synthesis, the alpha chain of the T cell antigen receptor (TCR alpha) can form a complex with other TCR chains and move to the cell surface, or TCR alpha can undergo degradation in the endoplasmic reticulum (ER) if it remains unassembled. The mechanism of translocation and degradation in the ER is unclear. It was found that the putative transmembrane region of TCR alpha (alpha tm) was incompetent on its own to act as a transmembrane region. Molecules that contained alpha tm were translocat

p62 is a novel immediate early response gene encoding a ubiquitin chain binding protein. To investigate the mechanism of p62 gene expression, we isolated and characterized the 20 kb long human p62 gene. The p62 gene contains seven introns and eight exons. The splice sites conformed to the GT/AG rule, except introns 6 and 7 which used the unusual GC dinucleotides. The p62 promoter is TATA-less, and 357 nucleotides of the 5'-flanking region contain basic machineries for transcription. A reporter g

PELP1 (proline-, glutamic acid-, and leucine-rich protein 1) has been recognized as a coactivator of estrogen receptor (ER)-recruiting p300/CREB-binding protein histone acetyltransferase to the target chromosome. The present study shows that PELP1 does indeed coactivate ER-mediated transcription but also serves as a corepressor of other nuclear hormone receptors (NR)- and non-NR sequence-specific transcription factors tested, including GR, Nur77, AP1, NF-κB, and TCF/SRF. PELP1 expression also re

It has been reported that prostate apoptosis response-4 (PAR-4) binds to and inhibits protein kinase Czeta (PKCzeta) which phosphorylates IkappaB kinase beta (IKKbeta) for nuclear factor kappaB (NFkappaB) activation, while p62 binds to and recruits PKCzeta to the NFkappaB signaling complex. Thus, a mechanism to coordinate the two binding proteins for the regulation of PKCzeta is expected to exist. The present data show that p62 and PAR-4 do not compete for PKCzeta binding but directly interact e

Adhesive interactions between multiple myeloma (MM) cells and marrow stromal cells activate multiple signaling pathways including nuclear factor kappaB (NF-kappaB), p38 mitogen-activated protein kinase (MAPK), and Jun N-terminal kinase (JNK) in stromal cells, which promote tumor growth and bone destruction. Sequestosome-1 (p62), an adapter protein that has no intrinsic enzymatic activity, serves as a platform to facilitate formation of signaling complexes for these pathways. Therefore, we determ

The T cell-specific tyrosine kinase, p56(lck), plays crucial roles in T cell receptor (TCR)-mediated T cell activation. Here, we report that SOCS-6 (suppressor of cytokine signaling-6) is a negative regulator of p56(lck). SOCS-6 was identified as a protein binding to the kinase domain of p56(lck) through yeast two-hybrid screening. SOCS-6 bound specifically to p56(lck) (F505), which mimics the active form of p56(lck), but not to wild type p56(lck). In Jurkat T cells, SOCS-6 binding to p56(lck) w