Larry Karnitz

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..However, new evidence suggests that most kinases do require chaperoning and, furthermore, that Cdc37, a chaperone that has Hsp90-dependent and -independent functions, serves as the chaperone for a large portion of the yeast kinome...

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..Collectively, our studies identify Chk1 as a novel Hsp90 client and suggest that pharmacologic inhibition of Hsp90 may sensitize tumor cells to chemotherapeutic agents by disrupting Chk1 function during replication stress...

..Taken together, these findings suggest that the 9-1-1 clamp is a multifunctional complex that is loaded onto DNA at sites of damage, where it coordinates checkpoint activation and DNA repair...

..In fact, Chk1 depletion reversed the sensitivity seen when Rad18 was disabled. Collectively, these studies suggest that the pharmacological manipulation of Chk1 may not be an effective strategy to sensitize tumors to platinating agents...

..Our data provide evidence for the existence of an alternative RFC complex with a probable role in mammalian sister chromatid cohesion establishment...

..Importantly, the cochaperones Hop and Cdc37 cooperate as the kinase transitions from immature Hsp70- to mature Hsp90-predominant complexes...

..Taken together, these results identify LATS1 and LATS2 as novel HSP90 clients and show that HSP90 inhibitors can disrupt the LATS tumor suppressor pathway in human cancer cells...

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..These results collectively suggest that S-phase-selective agents might exhibit more cytotoxicity when administered sequentially rather than simultaneously...

..Collectively, these results suggest that treatment with 17-AAG might represent a means of reversing checkpoint-mediated cytarabine resistance in AML...

..Collectively, these results show that the ATR/Chk1 pathway plays a predominant role in the response to topoisomerase I inhibitors in carcinoma cells and identify a potential approach for enhancing the efficacy of these drugs...

..Taken together, these results demonstrate that Cut5 plays an integral role in the recruitment and assembly of the Chk1 signaling cascade components following DNA damage...

..Collectively, these studies demonstrate that 9-1-1 chromatin binding is a proximal event in the checkpoint signaling cascade...

..Collectively, these results suggest that the predominant role of Rad9 in ES cells is to promote survival after replicative stress and topoisomerase-mediated DNA damage...

..Taken together, these results suggest that these proteins can combinatorially assemble into distinct 9-1-1 clamps that may have distinct biological functions...

..These results suggest that inappropriate Shh pathway activation promotes tumorigenesis by disabling a key signaling pathway that helps maintain genomic stability and inhibits tumorigenesis...

..Collectively, these results demonstrate that the Rad9 phospho-tail is a key participant in the Chk1 activation pathway and point to additional roles for Rad9 in cellular responses to IR...

..These reagents make the S-peptide/S-protein system an attractive alternative to currently available epitope tagging methods...

..Together, these data show that cell cycle checkpoint inhibitors may have significant clinical utility in potentiating the activity of gemcitabine...

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..Collectively, these studies will provide new insights into how the 911 complexes direct downstream events that regulate checkpoint activation, cell survival, and genomic stability. ..

..Collectively, these studies will provide information about the ability to alter the response of ovarian cancer cells to chemotherapeutic agents in vitro and in the clinical setting. ..

..Additionally, understanding the molecular details of this pathway will identify novel targets to sensitize cells to therapeutic DNA-damaging agents, such as ionizing radiation and anti-tumor chemotherapeutics. ..