MicroRNA-196a-5p is a potential prognostic marker of delayed lymph node metastasis in early-stage tongue squamous cell carcinoma.

MicroRNAs (miRs) are expected to serve as prognostic tools for cancer. However, many miRs have been reported as prognostic markers of recurrence or metastasis in oral squamous cell carcinoma patients. We aimed to determine the prognostic markers in early-stage tongue squamous cell carcinoma (TSCC).

Angiopoietin-like protein 2 induces proinflammatory responses in peritoneal cells.

Monocytes and macrophages are important effectors and regulators of inflammation, and both their differentiation and activation are regulated strictly in response to environmental cues. Angiopoietin-like protein 2 (Angptl2) is a multifaceted protein, displaying many physiological and pathological functions in inflammation, angiogenesis, hematopoiesis, and tumor development. Although recent studies implicate Angptl2 in chronic inflammation, the mechanisms of inflammation caused by Angptl2 remain unclear.

Smad inhibition by the Ste20 kinase Misshapen.

The level of TGF-β/bone morphogenetic protein (BMP) signaling through Smad is tightly regulated to ensure proper embryonic patterning and homeostasis. Here we show that Smad activation by TGF-β/BMP is blocked by a highly conserved phosphorylation event in the α-helix 1 region of Smad [T312 in Drosophila Smad1 (MAD)]. α-helix 1 phosphorylation reduces Smad interaction with TGF-β/BMP receptor kinase and affects all receptor-activated Smads except Smad3.

Ectopic coexpression of keratin 8 and 18 promotes invasion of transformed keratinocytes and is induced in patients with cutaneous squamous cell carcinoma.

Cutaneous squamous cell carcinoma (cSCC) results from transformation of epidermal keratinocytes. Invasion of transformed keratinocytes through the basement membrane into the dermis results in invasive cSCC with substantial metastatic potential. To better understand the mechanisms for invasion and metastasis, we compared the protein expression profiles of a non-metastatic transformed mouse keratinocyte line and its metastatic derivative.

Impact of human papillomavirus genotype on response to treatment and survival in patients receiving radiotherapy for squamous cell carcinoma of the cervix.

To determine the clinical implications and prognostic value of the human papillomavirus (HPV) genotype, we evaluated the various HPV types in patients receiving radiotherapy for squamous cell carcinoma of the cervix. The study population included 113 invasive squamous cell carcinoma patients treated with radiation or chemoradiation between 1993 and 2002. The median age of the patients was 61 years.

Regulation of Rap2A by the ubiquitin ligase Nedd4-1 controls neurite development.

Nedd4-1 is a "neuronal precursor cell expressed and developmentally downregulated protein" and among the most abundant E3 ubiquitin ligases in mammalian neurons. In analyses of conventional and conditional Nedd4-1-deficient mice, we found that Nedd4-1 plays a critical role in dendrite formation. Nedd4-1, the serine/threonine kinase TNIK, and Rap2A form a complex that controls Nedd4-1-mediated ubiquitination of Rap2A.

Caenorhabditis elegans FOS-1 and JUN-1 regulate plc-1 expression in the spermatheca to control ovulation.

Fos and Jun are components of activator protein-1 (AP-1) and play crucial roles in the regulation of many cellular, developmental, and physiological processes. Caenorhabditis elegans fos-1 has been shown to act in uterine and vulval development. Here, we provide evidence that C.

Rap2 function requires palmitoylation and recycling endosome localization.

Rap2A, Rap2B, and Rap2C are Ras-like small G proteins. The role of their post-translational processing has not been investigated due to the lack of information on their downstream signaling. We have recently identified the Traf2- and Nck-interacting kinase (TNIK), a member of the STE20 group of mitogen-activated protein kinase kinase kinase kinases, as a specific Rap2 effector.

MINK is a Rap2 effector for phosphorylation of the postsynaptic scaffold protein TANC1.

Rap1 and Rap2 are similar Ras-like G proteins but perform distinct functions. By the affinity chromatography/mass-spectrometry approach and the yeast two-hybrid screening, we identified Misshapen/NIKs-related kinase (MINK) as a novel Rap2-interacting protein that does not interact with Rap1 or Ras. MINK is a member of the STE20 group of mitogen-activated protein kinase kinase kinase kinases.

Proteomic analysis of rat retina in a steroid-induced ocular hypertension model: potential vulnerability to oxidative stress.

Purpose: To investigate global protein expression profiles in the retinas of normal and glucocorticoid-induced ocular hypertensive rats by proteomic analysis.

Methods: Ocular hypertension was induced by topical application of dexamethasone (DEX) for 4 weeks. Age-matched untreated rats served as controls.

Proteomic analysis of the trabecular meshwork of rats in a steroid-induced ocular hypertension model: downregulation of type I collagen C-propeptides.

Purpose: To investigate global protein expression profiles in the trabecular meshwork (TM) of normal and glucocorticoid-induced ocular hypertensive rat eyes by proteomic analysis, which has not yet been conducted to date.

Materials And Methods: A rat ocular hypertension model was produced by topical application of dexamethasone (DEX) for 4 weeks. Age-matched untreated rats served as controls.

A case of bullous congenital ichthyosiform erythroderma (BCIE) caused by a mutation in the 1A helix initiation motif of keratin 1.

Bullous congenital ichthyosiform erythroderma (BCIE) is an autosomally dominant inherited disorder characterized by erythematous, erosive, and bullous skin lesions over the entire body at birth and abnormal hyperkeratosis on the palmoplantar sufaces as the patient grows older. BCIE is caused by a mutation in the keratin 1 (K1) and/or keratin 10 (K10) genes, and most pathogenic mutations are found within the helix initiation and termination motifs of the central helical rod domain (K1 and K10) or the upstream H1 homology domain (K10). In addition to inherited cases, sporadic cases due to a new mutation account for approximately half the total cases of BCIE.

A genotype distribution of human papillomaviruses detected by polymerase chain reaction and direct sequencing analysis in a large sample of common warts in Japan.

There have been no large-scale epidemiological studies of human papillomavirus (HPV) genotype distribution of common warts in Japan. A total of 213 patients with common warts (104 males and 109 females) in Japan were studied to detect HPV genotype distribution by polymerase chain reaction (PCR) and direct sequencing analysis. The results were as follows: 94 HPV-1a (44.

Direct activation of fission yeast adenylyl cyclase by heterotrimeric G protein gpa2.

Genetic studies on Schizosaccharomyces pombe adenylyl cyclase (cyr1) have shown that its activity is positively regulated by a heterotrimetric G protein a subunit gpa2 and that the resulting increase in intracellular cAMP concentration causes inhibition of sexual development including mating and meiosis. However, molecular mechanism underlying this gpa2-dependent regulation of cyr1 remains to be clarified. Here, we show that gpa2 exhibits a direct and GTP-dependent binding to the Ras-associating domain (RAD) of cyr1, which is identified by a computer algorithm-based search of the cyr1 amino acid sequence.

PARG1, a protein-tyrosine phosphatase-associated RhoGAP, as a putative Rap2 effector.

Rap2 belongs to the Ras family of small GTP-binding proteins, but its specific signaling role is unclear. By yeast two-hybrid screening, we have found that the Caenorhabditis elegans ortholog of Rap2 interacts with a protein containing a Rho-GTPase-activating protein (RhoGAP) domain, ZK669.1a, whose human ortholog PARG1 exhibits RhoGAP activity in vitro.

Persistence of human papillomavirus infection as a predictor for recurrence in carcinoma of the cervix after radiotherapy.

Objective: This study was undertaken to examine a possible correlation between clearance or persistence of human papillomavirus (HPV) infection and radiation response in carcinoma of the cervix.

Study Design: We reviewed 97 patients with HPV-positive cervical squamous cell carcinoma (International Federation of Gynecology and Obstetrics [FIGO] stage IB-IVA) treated with radiotherapy. Examination of HPV DNA was performed by the polymerase chain reaction-based assay.

Phospholipase Cepsilon regulates ovulation in Caenorhabditis elegans.

Phospholipase Cepsilon (PLCepsilon) is a novel class of phosphoinositide-specific PLC with unknown physiological functions. Here, we present the first genetic analysis of PLCepsilon in an intact organism, the nematode Caenorhabditis elegans. Ovulation in C.

The Traf2- and Nck-interacting kinase as a putative effector of Rap2 to regulate actin cytoskeleton.

Rap2 belongs to the Ras family of small GTP-binding proteins, but its specific roles in cell signaling remain unknown. In the present study, we have affinity-purified from rat brain a Rap2-interacting protein of approximately 155 kDa, p155. By liquid chromatography tandem mass spectrometry, we have identified p155 as Traf2- and Nck-interacting kinase (TNIK).

A large case-control study of cervical cancer risk associated with human papillomavirus infection in Japan, by nucleotide sequencing-based genotyping.

Using nucleotide sequencing-based genotyping, we conducted a case-control study to examine cervical cancer risk associated with human papillomavirus (HPV) infection in a Japanese population. A consensus primer pair was used to amplify DNA from the L1 region of HPV by polymerase chain reaction (PCR). By PCR, 311 of 356 patients with cervical cancer and 333 of 3249 control individuals were positive for HPV.

Mitogen-activated protein kinase kinase kinase kinase 4 as a putative effector of Rap2 to activate the c-Jun N-terminal kinase.

Little is known about the specific signaling roles of Rap2, a Ras family small GTP-binding protein. In a search for novel Rap2-interacting proteins by the yeast two-hybrid system, we isolated isoform 3 of the human mitogen-activated protein kinase kinase kinase kinase 4 (MAP4K4), a previously described but uncharacterized isoform. Other isoforms of MAP4K4 in humans and mice are known as hematopoietic progenitor kinase (HPK)/germinal center kinase (GCK)-like kinase and Nck-interacting kinase, respectively.

Apoptotic effect in the glioma cells induced by specific protein extracted from Okinawa Habu (Trimeresurus flavoviridis) venom in relation to oxidative stress.

Okinawa Habu (Trimeresurus flavoviridis) venom is well known for its toxic efficacy, from which one kind of specific protein, Okinawa Habu apoxin protein-1 (OHAP-1) has been extracted. The purpose of this study was to investigate whether OHAP-1 could induce apoptosis in some glioma cells, and if so, to elucidate the possible mechanism involved. Three malignant glioma cell lines were tested.

Low-dose UVB contributes to host resistance against Leishmania amazonensis infection in mice through induction of gamma interferon and tumor necrosis factor alpha cytokines.

UV radiation suppresses the immune response, a fact which raises the question of whether the phenomenon may find practical applications in the outcome of infectious diseases. In this study, BALB/c mice were exposed to low-dose UVB (250 J/m(2)) from Dermaray M-DMR-100 for 4 consecutive days. Twelve hours after the last UV exposure, groups of mice were injected with 2 x 10(6) Leishmania amazonensis promastigotes.

Critical function of the Ras-associating domain as a primary Ras-binding site for regulation of Saccharomyces cerevisiae adenylyl cyclase.

Mammalian candidate effectors of the small GTPase Ras, such as RalGDS, afadin/AF-6, Rin1, and phospholipase Cepsilon, have been shown to share structurally conserved modules termed Ras-associating (RA) domains at their Ras-binding sites. The Ras-binding domains of Raf-1 and phosphoinositide 3-kinase gamma (other Ras effectors) also share a similar tertiary structure with the RA domains. On the other hand, the primary Ras-binding site of Saccharomyces cerevisiae adenylyl cyclase, the best characterized Ras effector, has been mapped by mutational studies to the leucine-rich repeats (LRR) domain (amino acids 674-1300), whose structure apparently bears no resemblance to the RA domains.