Identification of human cyclin-dependent kinase 8, a putative protein kinase partner for cyclin C.

Metazoan cyclin C was originally isolated by virtue of its ability to rescue Saccharomyces cerevisiae cells deficient in G1 cyclin function. This suggested that cyclin C might play a role in cell cycle control, but progress toward understanding the function of this cyclin has been hampered by the lack of information on a potential kinase partner. Here we report the identification of a human protein kinase, K35 [cyclin-dependent kinase 8 (CDK8)], that is likely to be a physiological partner of cyclin C. A specific interaction between K35 and cyclin C could be demonstrated after translation of CDKs and cyclins in vitro. Furthermore, cyclin C could be detected in K35 immunoprecipitates prepared from HeLa cells, indicating that the two proteins form a complex also in vivo. The K35-cyclin C complex is structurally related to SRB10-SRB11, a CDK-cyclin pair recently shown to be part of the RNA polymerase II holoenzyme of S. cerevisiae. Hence, we propose that human K35(CDK8)-cyclin C might be functionally associated with the mammalian transcription apparatus, perhaps involved in relaying growth-regulatory signals.

Gene for the catalytic subunit of the human DNA-activated protein kinase maps to the site of the XRCC7 gene on chromosome 8.

The DNA-activated serine/threonine protein kinase (DNA-PK) is composed of a large (approximately 460 kDa) catalytic polypeptide (DNA-PKcs) and Ku, a heterodimeric DNA-binding component (p70/p80) that targets DNA-PKcs to DNA. A 41-kbp segment of the DNA-PKcs gene was isolated, and a 7902-bp segment was sequenced. The sequence contains a polymorphic Pvu II restriction enzyme site, and comparing the sequence with that of the cDNA revealed the positions of nine exons. The DNA-PKcs gene was mapped to band q11 of chromosome 8 by in situ hybridization. This location is coincident with that of XRCC7, the gene that complements the DNA double-strand break repair and V(D)J recombination defects (where V is variable, D is diversity, and J is joining) of hamster V3 and murine severe combined immunodeficient (scid) cells.

Construction of a 2.8-megabase yeast artificial chromosome contig and cloning of the human methylthioadenosine phosphorylase gene from the tumor suppressor region on 9p21.

Many human malignant cells lack methylthioadenosine phosphorylase (MTAP) enzyme activity. The gene (MTAP) encoding this enzyme was previously mapped to the short arm of chromosome 9, band p21-22, a region that is frequently deleted in multiple tumor types. To clone candidate tumor suppressor genes from the deleted region on 9p21-22, we have constructed a long-range physical map of 2.8 megabases for 9p21 by using overlapping yeast artificial chromosome and cosmid clones. This map includes the type IIFN gene cluster, the recently identified candidate tumor suppressor genes CDKN2 (p16INK4A) and CDKN2B (p15INK4B), and several CpG islands. In addition, we have identified other transcription units within the yeast artificial chromosome contig. Sequence analysis of a 2.5-kb cDNA clone isolated from a CpG island that maps between the IFN genes and CDKN2 reveals a predicted open reading frame of 283 amino acids followed by 1302 nucleotides of 3' untranslated sequence. This gene is evolutionarily conserved and shows significant amino acid homologies to mouse and human purine nucleoside phosphorylases and to a hypothetical 25.8-kDa protein in the pet gene (coding for cytochrome bc1 complex) region of Rhodospirillum rubrum. The location, expression pattern, and nucleotide sequence of this gene suggest that it codes for the MTAP enzyme.

The EU, China and Southeast Asia: Divergent Views of Dealing with Human Security. Jean Monnet/Robert Schuman Paper Series Vol. 14 No. 8, May 2014

Introduction. This chapter takes a closer look at the European Union (EU), China, and the Association of Southeast Asian Nations (ASEAN)’s respective approaches to dealing with non-traditional security (NTS) challenges by investigating their policies toward Burma/Myanmar—a source country of numerous such challenges. It argues that, although all, as members of the ASEAN Regional Forum (ARF), see the need for multilateral solutions to fight organized crime, provide disaster relief, combat terrorism, prevent drug trafficking, etc., they differ with respect to the steps to be taken to protect human security in Asia-Pacific. China, initially hesitant to join the ARF for fear that other members might try to contain it, has come to value the principal forum for NTS challenges in the Asia-Pacific region since, like many ASEAN countries, it is a big proponent of non-interventionism, non-use of force, consensus decision-making, that is, the confidence-building mechanisms commonly referred to as the ‘ASEAN way’.2 The EU, as a strong proponent of human rights and the rule of law, repeatedly, has criticized ARF members for allowing sovereignty-related norms to get in the way of the protection of human rights, but it has refrained from assuming the role of norm exporter. As will be seen in the case of Burma/Myanmar, the EU does make its opinions heard and, when necessary, will take unilateral steps not supported by the ASEAN members of the ARF but, cognizant of the history of the region, for the most part, settles for supporting economic development and aiding in capacity-building, understanding that it would be counter-productive to exert pressure on reluctant ARF members to modify the non-interference norm. The chapter then speculates about the ‘ASEAN way’s’ longevity, arguing that, increasingly, there are internal and external dynamics that seem to indicate that the ‘ASEAN way,’ at least in its current form, may not be here to stay. The conclusion looks at what might be in store for Burma/Myanmar in the years to come.

Human rights in Nicaragua, Guatemala, and El Salvador : implications for U.S. policy : hearings before the Subcommittee on International Organizations of the Committee on International Relations, House of Representatives, Ninety-fourth Congress, second session, June 8 and 9, 1976.

Includes bibliographical references.

Hearing on child care [microform] : hearing before the Subcommittee on Human Resources of the Committee on Education and Labor, House of Representatives, One hundredth Congress, first session, hearing held in Washington, DC, on July 8, 1987.

"Serial no. 100-26."