scholarly journals Chromatin assembly factor 1, subunit A (P150) facilitates cell proliferation in human hepatocellular carcinoma

2016 ◽  
Vol Volume 9 ◽  
pp. 4023-4035 ◽  
Author(s):  
Meng Xu ◽  
Yuli Jia ◽  
Zhikui Liu ◽  
Linglong Ding ◽  
Run Tian ◽  
...  
2016 ◽  
Vol 45 (2) ◽  
pp. 739-748 ◽  
Author(s):  
Chunying Yang ◽  
Shiladitya Sengupta ◽  
Pavana M. Hegde ◽  
Joy Mitra ◽  
Shuai Jiang ◽  
...  

Author(s):  
Fatma M. Abd El-Salam ◽  
Entesar H. El-Sharqawy ◽  
Hala M. El-feky ◽  
Shuzan A. Mohammed ◽  
Ahmed M. Edres

Background: Hepatocellular carcinoma (HCC) is the third cause of cancer-related death worldwide. Heat Shock protein 60 (HSP60), a mitochondrial chaperone, is overexpressed in diverse malignant cells. Chromatin Assembly Factor-1 (CAF-1), a histone chaperone, is down-regulated in quiescent non-proliferating human cells. We aimed to clarify the role of HSP60 and CAF-1 mRNA expression in diagnosis of HCC post-HCV infection.Methods: HSP60 and CAF-1 mRNA levels in urine and blood were quantified by Taqman real-time PCR in 49 subjects; 25 cirrhotic with HCV-related HCC, 12 cirrhotic without HCC and 12 healthy controls.Results: HSP60 and CAF-1 mRNA levels in urine and blood were significantly higher in HCC versus cirrhosis and controls, and in cirrhosis versus controls. Their levels in HCC were significantly increased by advancement of HCC BCLC staging system. HSP60 in urine had 85% sensitivity and 66% specificity at cut off 258354 RU and 85% sensitivity and 60 % specificity at cut off 37576 RU in blood for HCC diagnosis. CAF-1 in urine had 81% sensitivity and 66% specificity at cut off 137756 RU and 77% sensitivity and 64% specificity at cut off 49726 RU in blood for HCC diagnosis. HSP60/CAF-1 sensitivity and specificity in urine and blood were better than either marker alone, with better results in urine (91% and 73%, respectively) than blood (88% and 66%, respectively).Conclusions: HSP60 and CAF-1 in urine and blood may be useful HCC diagnostic markers that were correlated with advancement of HCC with better combined marker sensitivity and specificity than either marker alone especially for urine.


2014 ◽  
Vol 25 (18) ◽  
pp. 2866-2881 ◽  
Author(s):  
Corey L. Smith ◽  
Timothy D. Matheson ◽  
Daniel J. Trombly ◽  
Xiaoming Sun ◽  
Eric Campeau ◽  
...  

Chromatin assembly factor-1 (CAF-1) is a three-subunit protein complex conserved throughout eukaryotes that deposits histones during DNA synthesis. Here we present a novel role for the human p150 subunit in regulating nucleolar macromolecular interactions. Acute depletion of p150 causes redistribution of multiple nucleolar proteins and reduces nucleolar association with several repetitive element–containing loci. Of note, a point mutation in a SUMO-interacting motif (SIM) within p150 abolishes nucleolar associations, whereas PCNA or HP1 interaction sites within p150 are not required for these interactions. In addition, acute depletion of SUMO-2 or the SUMO E2 ligase Ubc9 reduces α-satellite DNA association with nucleoli. The nucleolar functions of p150 are separable from its interactions with the other subunits of the CAF-1 complex because an N-terminal fragment of p150 (p150N) that cannot interact with other CAF-1 subunits is sufficient for maintaining nucleolar chromosome and protein associations. Therefore these data define novel functions for a separable domain of the p150 protein, regulating protein and DNA interactions at the nucleolus.


2007 ◽  
Vol 18 (1) ◽  
pp. 129-141 ◽  
Author(s):  
Yasunari Takami ◽  
Tatsuya Ono ◽  
Tatsuo Fukagawa ◽  
Kei-ichi Shibahara ◽  
Tatsuo Nakayama

Chromatin assembly factor-1 (CAF-1), a complex consisting of p150, p60, and p48 subunits, is highly conserved from yeast to humans and facilitates nucleosome assembly of newly replicated DNA in vitro. To investigate roles of CAF-1 in vertebrates, we generated two conditional DT40 mutants, respectively, devoid of CAF-1p150 and p60. Depletion of each of these CAF-1 subunits led to delayed S-phase progression concomitant with slow DNA synthesis, followed by accumulation in late S/G2 phase and aberrant mitosis associated with extra centrosomes, and then the final consequence was cell death. We demonstrated that CAF-1 is necessary for rapid nucleosome formation during DNA replication in vivo as well as in vitro. Loss of CAF-1 was not associated with the apparent induction of phosphorylations of S-checkpoint kinases Chk1 and Chk2. To elucidate the precise role of domain(s) in CAF-1p150, functional dissection analyses including rescue assays were preformed. Results showed that the binding abilities of CAF-1p150 with CAF-1p60 and DNA polymerase sliding clamp proliferating cell nuclear antigen (PCNA) but not with heterochromatin protein HP1-γ are required for cell viability. These observations highlighted the essential role of CAF-1–dependent nucleosome assembly in DNA replication and cell proliferation through its interaction with PCNA.


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