| Title | Description | Published | Added |
| The three Jameses | | 1962 | 2025-05-22T16:21:27Z |
| I was a probationer | | 1937 | 2025-09-08T07:44:38Z |
| Second international meeting of the international society for neurochemistry | | 1969 | 2025-09-08T04:17:18Z |
| Irradiation And The Nervous System | | 1963 | 2025-09-11T15:24:38Z |
| Flight Without Power | | 1940 | 2025-09-12T12:32:24Z |
| Authenticom, Inc. v. CDK Global, LLC | This item represents a case in PACER, the U.S. Government's website for federal case data. This information is uploaded quarterly. To see our most recent version please use the source url parameter, linked below. To see the canonical source for this data, please consult PACER directly. | | 2020-03-25T23:18:28Z |
| Two Kinds of Time: Life in Provincial China During the Crucial Years 1940-1941, Revised and Abridged | | 1967 | 2023-12-23T07:35:21Z |
| AD #3841 - Rivian Hits Paydirt With Massive VW Investment; Revealed The Last Pontiac Concept Car; CATL Flies 4-Ton Electric Plane | - Rivian Hits Paydirt With Massive VW Investment- Rivian Hints At 5 Future Models- Tesla Drops Under 50% U.S. EV Market Share- CDK Cyberattack Lasts Longer Than Expected- U.S. June Sales At 16.2 Million SAAR- Revealed The Last Pontiac Concept Car- GM-SAIC Use Robots for Car Testing- Bentley Unleashes Most Powerful Model Ever- CATL Flies 4-Ton Electric Plane | 2024 | 2024-11-16T18:41:55Z |
| Mannen Med Salgpiporna | | 1960 | 2025-09-26T02:02:52Z |
| Research in physiology | | 1971 | 2025-09-08T00:26:07Z |
| Scientists In Organizations | | 1966 | 2025-09-11T18:21:23Z |
| De Racine Au Parthenon: Essais Sur La Litterature Et L'Art A L'age Classique | | 1977 | 2025-09-04T14:43:38Z |
| Aviles v. CDK Global, LLC | This item represents a case in PACER, the U.S. Government's website for federal case data. If you wish to see the entire case, please consult PACER directly. | | 2024-06-28T09:07:16Z |
| Predictive value of progesterone receptor in advanced-stage breast cancer patients treated with CDK 4/6 inhibitors | ABSTRACT Aims: Phase III studies investigating CDK 4/6 inhibitors have failed to identify significant predictive or prognostic markers that aid clinicians in therapeutic decision-making. Given the complex treatment landscape in breast cancer, identifying patient and tumor characteristics that optimize the utilization of CDK 4/6 inhibitors across diverse therapeutic approaches is crucial. In our study, we aimed to evaluate the predictive role of progesterone receptor (PR) expression levels in patients with estrogen receptor (ER)-positive and human epidermal growth factor receptor 2 (HER2)-negative advanced-stage breast cancer treated with CDK 4/6 inhibitors. Methods: This study retrospectively evaluated 244 patients who received a combination of CDK 4/6 inhibitors and endocrine therapy as their first-line treatment. Those with PR levels below 20% were designated as low PR expression patients, and those with levels of 20% or above were classified as high PR expression patients. These two; | 2025 | 2025-08-14T08:44:59Z |
| Living embers: the life and writings of George William Griffith | | 1937 | 2023-12-28T00:31:16Z |
| CKD (28648) | CDK logo | 2012 | 2021-04-02T02:54:24Z |
| DTIC ADA359281: Role of the Cdk Inhibitor Sic 1 in Start | Mpst cells have four fundamental goals; they must replicate their DNA, segregate their chromosomes, double their mass, and divide. Coordination of these events is essential. I have used the budding yeast S. cerevisiae to dissect the molecular events that control cell cycle progression. I have shown that not only are G1 cyclin-CDK complexes highly unstable rate-limiting activators for cell cycle progression, but that their essential function is to regulate the initiation of DNA replication by phosphorylating and promoting the degradation of a key cell cycle inhibitor, Sic1 (1,2). In fact, cyclin-CDK-regulated proteolysis may constitute the major mechanism of cell cycle control (3). Moreover, Sic1 appears to be the analog of the RB tumor suppressor gene. I have shown that Sic1, like RB, controls the timing of S-phase, ensures genomic stability, and most significantly, sic1 deletions, like rb deletions, completely remove cell cycle dependence on G1 cyclins (1,22). Furthermore, Sic1 protei; | 1998 | 2018-04-21T20:11:43Z |
| yahoo-groups-2018-07-21T22-47-06Z-4bbc23 | Yahoo! Groups API grab. Contains messages of the following groups: 1ahoahong 2009cmsc128 abajarcolesterol abqphilosophers aceng1-ib agentorangeveterans alumnisaba93 ap12thv1 apn_maamvanne aquascape-indonesia arabic_inside arkiyoliji1 artsbabes asteric_of_smpn4_bogor ba186_sad bch_tongdoan_2008_2010 beginnerbluegrassjam biblebeegurnee binjakon bits_dlpd_msss2009 blogbirudotcom bsa_bag bspe1-1_economist ca411-1m canoepolohunks0809 ccfcommittee_09_10 che_141_142_tqruv chem2a_woodland cict_itfnds-icb citihi85 contratoscinemauff cool_hood_babii cpi_2009_2010 csci12_tz curriculoseprogramas2009essb dbti_tarlac_faculty discretemath_it2nd dmt_people dnyandeepnews dpms_2010 ec102h eco101_09 eco11_0910 ecoprofessionals_nea edp111_addu elladerma emc_ss_dames encoreestate esjsem1admu0910 galeradoingles2008 genevaacademicfoundation glawenko h-383lpu hau_6comgrad hiltech_group homplantes hum1_thu1 iit-kgp-met75 imtak-05 infoamie ingenieria_gay inspirationaldesignsvoices irc-sbg ironbros-team_one it10; | | 2018-07-21T22:47:14Z |
| Ultimate Mortal Kombat 3: (BR) [CDK]-heldinho vs(BR) [CDK]-Chakality - 2022-04-03 01:22:00 | (BR) [CDK]-heldinho vs (BR) [CDK]-Chakality - 2022-04-03 01:22:00 Fightcade replay id: 1648948920772-7644 #fightcade #umk3 #[CDK]-heldinho #[CDK]-Chakality For more videos check out: https://fightcadevids.com | | 2022-07-24T22:02:35Z |
| Street Fighter Alpha 2 (960430 USA): (BR) [CDK]-Shaka vs(BR) SweetG - 2022-08-22 04:08:29 | (BR) [CDK]-Shaka (Rank D) vs (BR) SweetG C - 2022-08-22 04:08:29 Fightcade replay id: 1661141309737-2933 0:00 Ryu vs Sagat 02:38 Ryu vs Dan 04:15 Dan vs Sagat 06:25 Evil Ryu vs Dan 08:19 Dan vs Zangief #fightcade #sfa2u #0:06:25 #[CDK]-Shaka #SweetG #0:08:19 #Sagat #Zangief #0:02:38 #0:00:10 #Dan #0:04:15 For more videos check out: https://fightcadevids.com | | 2023-01-23T15:42:54Z |
| CDK Global Holdings, LLC v. Tekion Corp. | This item represents a case in PACER, the U.S. Government's website for federal case data. If you wish to see the entire case, please consult PACER directly. | | 2025-02-11T10:29:53Z |
| Asian economy ppt CDK | Spoken text for ppt asian economy CDK | | 2011-04-03T16:27:54Z |
| Various Artists * 33,333 Steps To A Power Ov The Darkness Leagues | Various Artists * 33,333 Steps to a Power ov the Darkness Leagues (Disc one) 01. DJ R3V3R3ND MURD3R * !33,333 STEPS TO A POWER OV THE DARKNESS LEAGUES! 02. sOuL_sCientiSt * More Fiyah Mix 03. FIGURATIVE THEATRE * MEGAMARKET UTOPIA 04. Hel.Razor * Slave 2 The System 05. dreDDup * We Fuck Until Dawn 06. Moray Eel * Hellish Adoption 07. Cryogenic Implosion * Delete Humanity 08. The Apocryphal Order * Beyond The Depraved Scope Of Salvation 09. Come To My Rise * Play A Game 10. The Rinn * Voices 11. Crimson Blue * L.M.A. 12. Severed Fifth * Blackening 13. Spiritual Dissection * Across A Frozen Hell 14. Returning We Hear the Larks * Nascence in the Caverns of Mount Olympus 15. Cuntworm * Seduced By Damnation 16. Earslaughter * Roka Smrti (Disc two) 01. DiSloCaTed * Megazord 02. Cyber Snake * War 03. Circlerun * 13 04. Obsidian Shell * Misanthropia 05. Dawn Of Tears * Since They're Gone 06. Operación Mutante * Matanza 0; | 2013 | 2013-11-26T13:29:39Z |
| Historic Preservation Awards 2013 | | 2013 | 2016-10-07T01:03:50Z |
| [CDK 040] Buskerdroid – Mnemonic Backup | [CDK 040] Buskerdroid – Mnemonic Backup | 2009 | 2020-01-05T18:13:48Z |
| [CDK 063] The Tin Foil Hat Brigade - Serious Musician | Unrequited love, the frustrations of modern life, Scallies shouting abuse at women from cars - The Tin Foil Hat Brigade talks about these, and more - all within a ten-minute blast of furious Game Boy noise and raw, emotional vocals. Or something like that, anyway. All Music and Lyrics by The Tin Foil Hat Brigade. Recorded and Mastered by Lloyd Gabriel. Additional Vocals (on G.Y.R.O) by Simon Patrick Gabriel and Lloyd Gabriel. Artwork and Photography by Simon Thelwell - http://www.sixeightthree.com/ | 2014 | 2020-01-09T22:58:35Z |
| CE QUE LES FEMMES AIMENT CHEZ LES HOMMES ? [MICRO-TROTTOIR] | Le 19 novembre, c'est la journée internationale de l'homme. A cette occasion, Alexis Fontana et moi-même avons demandé aux femmes quelles qualités elles souhaitaient particulièrement célébrer chez les hommes. Nous avons ensuite réalisé une petite conclusion visible sur sa chaîne : https://www.youtube.com/watch?v=pmlLsIXePQ8 - Découvrez la chaîne d'Alexis Fontana, qui milite pour les droits des hommes, et abonnez-vous : https://www.youtube.com/channel/UCoUymjC2BXspKoraaEzlisw/videos - Alexis Fontana a consacré une autre vidéo à la Journée internationale de l'homme : https://www.youtube.com/watch?v=VO_j4UEIElI - Célébrez les qualités des hommes ! https://www.droitsdesgarcons.fr/journee-mondiale-des-hommes/ - Voir la pétition sur Change.org: https://www.change.org/p/macron-o%C3%B9-sont-les-hommes-dans-%C3%A9galit%C3%A9-hommes-femmes ► Soutenez mon travail et cette chaîne... Merci à vous ! : https://www.tipeee.com/virginie-vota | 2018 | 2023-06-02T18:42:51Z |
| The King of Fighters 2002: (BR) LZO//GOIANO CAPOEIRA vs(BR) [CDK]-Shaka - 2022-12-26 14:01:27 | (BR) LZO//GOIANO CAPOEIRA vs (BR) [CDK]-Shaka - 2022-12-26 14:01:27 Fightcade replay id: 1672063287929-7484 #fightcade #kof2002 #LZO//GOIANOCAPOEIRA #[CDK]-Shaka For more videos check out: https://fightcadevids.com | | 2022-12-28T21:17:04Z |
| AD #3839 - China to EU, Drop Tariffs...Or Else; China Car Exports Up 26% In 2024; Ford, Rivian and Hyundai EVs Tackle Pikes Peak | - China to EU, Drop Tariffs...Or Else- China Car Exports Up 26% In 2024- Russia Car Dealers Upset at Chinese OEMs- Cyberattack Still Disrupting Car Dealers- Bosch #1 Auto Supplier Last Year- Ford, Rivian and Hyundai EVs Tackle Pikes Peak- Ferrari Launches New Facility to Make EVs- F1 and Amazon Use Generative AI to Enhance Race Broadcasts- China Car Execs Turn to Livestreaming to Lure Customers | 2024 | 2024-11-16T18:59:36Z |
| Cyber Flash Point. Devastating Ransomware Attack on Auto Industry. CDK Global. | In today's cyber flash point, we show you how to digest recent data breaches and how to take action against cyber crime.Have you ever wondered how a single cyberattack can cripple an entire industry? Or how businesses can recover from such a devastating blow? Ever realize the cyber security risks from SaaS platforms? Today we dive into the gripping tale of the ransomware attacks on CDK Global, a leading provider of dealer management systems (DMS) for car dealerships across North America. Send us a textHave a Guest idea or Story for us to Cover? You can now text our Podcast Studio direct. Text direct (904) 867-446?? Subscribe now http://www.youtube.com/@cybercrimejunkiespodcast and never miss an episode! Follow Us: ?? Website: https://cybercrimejunkies.com?? X/Twitter: https://x.com/CybercrimeJunky?? Instagram: https://www.instagram.com/cybercrimejunkies/Want to help us out? Leave us a 5-Star review onApple Podcast Reviews. Listen to Our Podcast:??️ Apple Podcasts: https://podcasts.a; | 2024 | 2024-11-14T06:46:45Z |
| DTIC ADA389310: Regulation of Ubiquitin Mediated Proteolysis of G1 Cyclins and the CDK Inhibitor p27 by the Cullin Gene Family in Normal and Tumorigenic Human Breast Cells | The periodicity of CDK activity provides the molecular basis for unidirectional cell cycle progression and is partly controlled by ubiquitin-mediated proteolysis of both cyclins and CDK inhibitors. Deregulated expression of G1 CDK inhibitors and G1 cyclins has been directly linked to breast cancer development. The mechanisms regulating the ubiquitination of these two protein families constitute essential components of G1 cell cycle control in mammalian cells. Polyubiquitination of proteins is known to be catalyzed by a cascade of enzymes: E1 (ubiquitin activating), E2 (ubiquitin conjugating), and E3 (ubiquitin ligating). Two issues critical to our understanding of the regulation of protein turnover are how E3 ligases target proteins for ubiquitination and how they themselves are regulated. We have found that cullins partner with another multigene family of evolutionarily conserved proteins, the ROC/APC11 family, to form a complex that contains E3 ubiquitin ligase activity. We have show; | 2000 | 2018-05-01T22:46:59Z |
| DTIC ADA388443: Development and Use of Novel Tools to Directly Screen for Substrates of Cyclin Dependent Kinases | The aim of this research is to gain further insights into the means by which cell proliferation is controlled by cyclin dependent kinases. To this end, a screen has been carried out for proteins that interact with the budding yeast cdk, Cdc28. 10 novel interacting proteins have been identified in a two-hybrid screen using a Gal4/Cdc28 fusion as the bait. Several of the putative interacting proteins have been shown to interact with specific cyclin-Cdc28 kinase complexes. For each of the 10 two-hybrid positives the nature of the Cdc28 interaction is currently being determined by biochemical means. The functional difference between cyclins in their abilities to induce and repress transcription has been investigated using the genomic technology of microarrays. In addition, the complete set of cell cycle regulated genes in yeast has been defined. This work has now been published (MBC 9:3273-3297 1998), and a full description and complete data sets are available on a public website at http:/; | 2000 | 2018-05-01T07:37:13Z |
| DTIC ADA366910: Interaction of the Tumor Suppressor p53 With Replication Protein A. | In order to understand how the tumor suppressor p53 blocks the cell-cycle at the G1-S transition we studied how p21, a transcription target of p53, interacts with and inhibits cyclin-dependent kinases (cdk). We identified specific cyclin-binding Cy motifs on the p21 molecule that were essential for docking p21 on cyclin-cdks and discovered that such Cy motifs were present and functional on substrates and activators of cdks. This year we discovered the presence of a Cy motif on a newly identified human DNA replication initiation factor, Cdc18. This Cy motif is required for the stable association of Cdc18 with cyclin A-cdk2 in vivo. Wild type Cdc18 is in the nucleus at G1 and removed from the nucleus at S phase once cyclin-cdks are activated. The Cy motif of Cdc18 is necessary for this S phase specific removal of nuclear Cdc18 implying that Cdc18 is a physiological substrate of cyclin-cdks at the G1-S transition. | 1998 | 2018-04-24T22:32:17Z |
| DTIC ADB231798: Biochemical Characterization of Complexes with p21, a CDK Inhibitor | The cyclin-dependent kinases (CDKs) are of pivotal importance for driving cell proliferation. The p2l/WAFl protein, by contrast, belongs to a family of growth regulators that are thought to restrain cell growth primarily as a consequence of their ability to inhibit CDKs. In vivo, p2l is known to form stable, higher order complexes with cyclin-dependent kinases and the DNA polymerase processivity factor, PCNA. As an important downstream target of the p53 checkpoint gene, p21 is thought to execute a critical growth arrest function in response to DNA damage and other cellular stress and differentiation signals. In addition, loss of p21 function may be associated with cellular transformation in some settings. Despite this information, it is not yet clear how p21 functions in vivo to regulate the multiple complexes with which it associates. Nor is it clear how p21 specifically regulates CDKs in vivo or whether all components of p21 complexes have been identified. Given the role of p21 and r; | 1997 | 2018-02-28T13:39:40Z |
| Laraqua's Masks Of Nyarlathotep Prologue | The prologue for my Masks of Nyarlathotep solo game designed to get the protagonist to New York ready for the Half-Moon Cult adventure followed by Masks itself. More information on the campaign can be found, including Easter Eggs during the various sessions and a little context, can be found under the Masks of Nyarlathotep tag on http://stwildonroleplaying.blogspot.com.au/ The opening music is CDK's Sunday Sunrise which is Creative Commons (Attribution 3.0) and can be found at http://ccmixter.org/files/cdk/13613 Episode 3's subway soundtrack is Public Domain material which can be found at the Soundbible at http://soundbible.com/386-Riding-NYC-Subway-Car.html | 2013 | 2013-11-24T21:58:36Z |
| DTIC ADA412764: Use P27KIP1 Degradation for Breast Cancer Diagnosis and Therapy | P27 IS A CDK inhibitor that controls the Gl/S transition. Low or absent expression of p27 has been observed in many malignant tumors including breast cancer. SCF(SKP2) is a ubiquitin E3 ligase that interacts and targets p27 for ubiquitin-dependent proteolysis. One aim of the proposal is to determine whether there is an inverse relationship between SCF(SKP2) and p27 in breast cancer and the experiments are in progress. Another aim is to determine the domain on SKP2 that binds to p27. We have determined the carboxy-terminal region of SKP2 is required for binds to phosphorylated p27. The critical aim is to determine whether inhibition of SCF(SKP2) in breast cancer cells causes cell cycle arrest. Our studies suggest that inhibition of SCF(SKP2) in breast cancer and other cancer cells causes accumulation of p27 and Gi cell cycle block. Thus SCF(SKP2) may be used as a target for breast cancer therapy. | 2002 | 2018-05-12T16:38:48Z |
| DTIC ADA323678: General Methods for Identifying G1-Phase Substrates of Cdk Protein Kinases. | We are using two-dimensional gels in combination with genetic and biochemical techniques to identify G1-phase substrates of cyclin-Cdk complexes. We have optimized protocols for labeling proteins with 32P prior to two-dimensional gel electrophoresis. So far, we have successfully identified one important in vivo substrate, Sic1. We have characterized Sic1, and have shown that phosphorylation of Sic1 by cyclin-Cdk complexes promotes DNA synthesis in yeast. We have made peptide antigens for the purpose of making antibodies against phosphorylated Cdk substrates. Mice have been immunized; their sera are positive; and fusions for monoclonal antibodies are about to be done. | 1996 | 2018-04-05T02:36:00Z |
| Bob Baker Volkswagen v. CDK Global, LLC | This item represents a case in PACER, the U.S. Government's website for federal case data. This information is uploaded quarterly. To see our most recent version please use the source url parameter, linked below. To see the canonical source for this data, please consult PACER directly. | | 2018-09-16T22:44:00Z |
| The Old Architecture of Quebec | | 1947 | 2025-05-22T17:20:02Z |
| Reaganautas III | Olvidemos lo no grabado y lo no publicado y centrémonos en lo que sà podemos escuchar. En esta ocasión, y siguiendo nuestra absurda costumbre de colgar programa sÃ, programa no, tenemos la tercera muestra audible de la mayor locura de las ondas herzianas. John Randall Hoth analiza la victoria de los Republicanos en las elecciones legislativas estadounidenses y toda la actualidad sobre la senadora zombie, Jerry Conway nos acerca a un mito del rock underground, CDK Pichafrita, con la visita de Lucas, uno de los que fueran componentes del grupo y Jimmy Weaver se adentrará en las redes de nuestro querido Tea Party. Acontecimiento: se produce la primera llamada telefónica al programa y todo ello tras la irrupción de la policia en el estudio buscando un perro kamikaze enviado desde Grecia. | | 2010-11-04T23:12:52Z |
| The reason you can't buy a car is the same reason that your health insurer let hackers dox you | This week on my podcast, I read The reason you can't buy a car is the same reason that your health insurer let hackers dox you , a column from one of last week's editions of my Pluralistic newsletter; it describes a monopoly pattern whereby companies execute a series of mergers to dominate a sector, leaving their IT systems brittle and tangled - and vital to the nation. Just like with Equifax, the 737 Max disasters tipped Boeing into a string of increasingly grim catastrophes. Each fresh disaster landed with the grim inevitability of your general contractor texting you that he's just opened up your ceiling and discovered that all your joists had rotted out – and that he won't be able to deal with that until he deals with the termites he found last week, and that they'll have to wait until he gets to the cracks in the foundation slab from the week before, and that those will have to wait until he gets to the asbestos he just discovered in the walls. Drip, drip, drip, as you realize th; | 2024 | 2024-06-30T21:51:55Z |
| Congenital Dislocation of the Knee in a Newborn | Congenital dislocation of the knee (CDK) is a relatively rare condition with an estimated prevalence of 1 per 100 000 live births, which is approximately 1% of the incidence of developmental dysplasia of the hip1. It may occur in isolation, but often occurs in the presence of muscle imbalance such as that seen with arthrogryposis, Larsen syndrome, and myelomeningocele. CDK has also been reported to occur with other musculoskeletal abnormalities including developmental hip dysplasia, clubfoot, congenital vertical talus, and congenital dislocation of the elbow2. | 2020 | 2024-05-09T10:25:38Z |
| DTIC ADA453395: Suppression of Prostate Cancer by PTEN and p18INK4c | The Rb pathway suppresses tumorigenesis by constraining G1 cell cycle progression. Functional inactivation or reduction of this pathway is a common event found in many types of human tumors. To test how the Rb pathway interacts with other cellular pathways in tumor suppression, we characterized mice with combined mutations in the CDK inhibitor p18 (exp Ink4c) and the lipid phosphatase PTEN, which regulates cell growth and survival. The p18(exp -/-) ; PTEN (exp +/-) double mutant mice develop prostate cancer in the anterior and dorsolateral lobes and thyroid C-cell tumors with nearly complete penetrance, and pituitary tumors in both the anterior and intermediate lobes. AKT/PKB, an oncoprotein and downstream substrate of PTEN, was activated and accumulated at the plasma membrane in PTEN (exp +/-) cells, and further activated and accumulated in the nucleus in p18 (exp -/-) ; PTEN (exp +/-) tumor cells, suggesting a tissue- and genetic background-dependent haploinsufficiency of Pten in tum; | 2006 | 2018-06-05T18:22:11Z |
| DTIC ADA300399: Functions of Wild-Type and Mutant Forms of p53 in Breast Cancer. | Cells induced to accumulate the p53 tumor suppressor protein have been shown to arrest in G1. This arrest is characterized by accumulation of the cyclin dependent kinase (CDK) inhibitor p2l (WAF1/CIP1) and of underphosphorylated forms of retinoblastoma protein (pRB). We show here that accumulation of the wild-type pS3 protein in either human or murine cells markedly increases expression of cyclin Dl. The induction of cyclin Dl can also be mediated by a target of p53, the p21 (WAF1/CIP1) inhibitor of cyclin-dependent kinases. The relationship between the induction of cyclin Dl and G1 arrest defines a new cellular response to p53. | 1995 | 2018-03-24T09:25:56Z |
| DTIC ADA398199: Regulation of Ubiquitin Mediated Proteolysis of G1 Cyclins and the CDK Inhibitor p27 by the Cullin Gene Family in Normal Tumorigenic Human Breast Cells | Ubiquitin-mediated proteolysis of cyclins, cyclin-dependent kinase inhibitors and certain other substrates, including proteins whose degradation is necessary for progression through mitosis, provide a molecular basis for unidirectional progression through the eukaryotic cell cycle. Aberrations in the ubiquitin-mediated destruction pathways, and particularly in the destruction of the Dl cyclin, have been implicated in human breast cancer. A cascade of enzymes leads to ubiquitination of substrate: El enzyme (ubiquitin activating); E2 enzyme (ubiquitin conjugating), and E3 enzyme (ubiquitin ligase). This last class of enzyme is large, and it performs the functions of targeting substrate and catalyzing formation of the polvubiquitin chains that mark substrate for destruction. We have found that all three members of the yeast cullin family are capable of performing the ubiquitination activity of E3 enzyme. All three yeast cullins undergo covalent modification with Rub1 protein, presumably t; | 2001 | 2018-05-05T21:00:08Z |
| DTIC ADA412793: Chemotherapy of Late Stage Breast Cancer Targeted Towards Cell Cycle Regulatory Components | Our original goal was to target cell cycle regulatory components as a potential therapy for breast cancer. The target p16 is a tumor suppressor and a CDK inhibitor and is inactivated by gene methylation. The drug 5-aza-2'deoxycytidine (5-Aza-CdR), an inhibitor of DNA methylation, is targeted for reexpression of a repressed p16 in late stage breast cancer patients. Re-activation of the p16 gene in cells in which the gene is methylated will restore normal growth control and be efficacious in treatment of breast cancer. A mouse model for the action of the drug was developed and used to test the efficacy of the drug. | 2002 | 2018-05-12T16:53:07Z |
| DTRASH10 - Bastards United - Bastards United | This is a killer collection of breakneck headbanger digital thrash music. Bastards United have are a complete digicore band with guitarists, MCs and program thrashers. Straight from the Netherlands, BU collaborates on some slammin' tracks with Rabies/CDK and b57 from CPUWAR in the mix! | 1999 | 2008-04-19T16:24:14Z |
| DTIC ADA382749: Resistance to Tamoxifen: A Consequence of Altered p27Kipl Regulation During Breast Cancer Progression | This grant addresses the molecular mechanisms of resistance to the anti-estrogen, Tamoxifen, in breast cancers. Both estrogens and antiestrogens influence the cell cycle during the GI phase. In breast tumors, loss of the cdk inhibitor, p27, is associated with a poor prognosis and with steroid resistance. We postulate that altered p27 degradation in breast cancer may contribute to resistance to antiestrogen therapy. In the last year, we have assayed cell cycle effects of estradiol in the ER+ breast cancer cell line, MCF-7. MCF-7 arrests in G1 upon removal of estradiol or on addition of Tamoxifen. Upon re-addition of estradiol, cells re-enter the cell cycle with onset of S phase by 12 hours and loss of both p21 and p27 proteins. Cyclin D1 associated kinase activity rose transiently in early G1. Activation of cyclin E/cdk2 kinase in mid-late G1 was accompanied by loss of cyclin E-associated p21 and p27. The requirement for p27 in the quiescence induced by estradiol depletion was investiga; | 1999 | 2018-04-29T17:57:19Z |
| DTIC ADA430444: Targeting the AP-1 Transcription Factor for the Treatment of Breast Cancer | The AP-1 transcription factor is a central component of many signal transduction pathways. We have shown that blocking AP-1 by over-expressing a dominant negative form of cJun (cjun-DN, Tam67) inhibits breast cancer cell growth. We hypothesize that inhibition of AP-1 blocks the cell cycle, suppression of AP-1 in vivo inhibits the development of breast tumors, the cjun-DN protein binds and inactivates important growth regulatory proteins present in breast cancer cells, these proteins include Jun and Fos family members as well as coactivators that bind cJun. In the present study, we demonstrated that TAM67 inhibits breast cancer growth both in vitro and in vivo. We determined the mechanism by which AP-1 blockade inhibits breast cancer growth. Our studies suggested that TAM67 inhibits breast cancer growth predominantly by inducing CDK inhibitors ?such as P27), suppressing G1 cyclins expression and reducing CDKs activity, thus inducing a cell cycle block. We also showed that TAM67 binds al; | 2004 | 2018-05-23T22:15:58Z |
| DTIC ADA386459: Action of the p53 Effector, p21, on its Targets: Cyclin-CDK & PCNA | Our aim is to dissect the interactions of p21 (a downstream effector of the tumor suppressor protein p53) with its targets, cyclin-cdks and PCNA. In year 2 we have focused on the cyclin-cdks. We have quantitated the contribution of the cyclin-cdks binding Cy motif (on cdk substrates) to their interaction with the cyclin-cdks. We find that a Cy motif improves the Km of a substrate by 5OO-1000 fold without any effect on the Vmax of the peptide or the Km of ATP. Such a large contribution of the Cy motif to substrate recognition explains why a peptide based on the Cy motif of p21 inhibits phosphorylation by cdk. A small chemical that mimics the structure of the Cy motif would be a specific inhibitor of cdks and suppress breast cancer cell growth. Towards this end, site directed mutagenesis has been used to generate a library of mutants in the Cy motif of p21. Using this library we find that the first arginine (R1) and the third leucine (L3) of the Cy motif (RRLFG) are critical for docking ; | 1999 | 2018-04-30T22:37:50Z |