Enhanced deacetylation of p53 by the anti-apoptotic protein HSCO in association with histone deacetylase 1
Authors: Katsuhiko Itoh
Hiroaki Higashitsuji
Tomoko Masuda
Yu Liu
Hisako Higashitsuji
Jun Fujita
Journal: Journal of Biological Chemistry (2007)
Discipline: BIOLOGY & BIOCHEMISTRY
Keywords: HSCO; NF-kappaB; anti-apoptotic; p53; Noxa
Affiliations: Department of Clinical Molecular Biology, Graduate School of Medicine, Kyoto University, 54 Shogoin Kawaharacho, Kyoto 606-8507, Japan.

Abstract:  HSCO (hepatoma subtracted-cDNA library clone one, also called ETHE1) was originally identified by its frequent overexpression in hepatocellular carcinomas. HSCO inhibits function of NF-kappaB by binding to RelA and accelerating its export from the nucleus. We show here that HSCO exhibits anti-apoptotic activity in cells exposed to DNA-damaging agents by suppressing transcriptional activity of p53. Induction of pro-apoptotic genes, Noxa, Perp, PIG3, and Bax were suppressed in cells over-expressing HSCO. By increasing ubiquitylation and degradation of p53, HSCO reduces p53 protein levels. HSCO specifically associates with histone deacetylase 1 (HDAC1) independently of Mdm2 and facilitates deacetylation of p53 at Lys-373/382 by HDAC1. The metallo-beta-lactamase family consensus sequence in HSCO is important for its effect on p53 deacetylation. Co-immunoprecipitation and immunofluorescence studies suggested that HSCO, HDAC1, and p53 form a complex in the nucleus. Thus, HSCO is a cofactor that increases the deacetylase activity of HDAC1 toward p53, leading to suppression of apoptosis. Treatment of hepatocellular carcinomas that retain wild-type p53 and overexpress HSCO with anti-HSCO agents might re-establish the p53 response and revert chemoresistance. 

Retracted: No

PubPeer comments:
 The immunoblot for Ac-p53 in green boxes appear to look similar in Fig 5B. The immunoblot for p53 in red boxes appear to look like they came from the same one. The bands have been flipped and stretched. ![file] , 
 #1 #1 Dear Lucinisca, Thank you for your comment. I agree with you. I did not notice it. It is quite strange to use the same pictures in one figure, and I am embarrassed. This is a shame. As I have no means to check the original data, I will retract the paper. I retired 6 years ago, no former lab, and it may take some time to contact the former collaborators. Regards, Jun , 
 #2 Dear Lucinisca, I have noticed that this Fig. 5B does not show data of Ac-p53(Lys320) for lanes 7-10, indicating that this is not the final Fig. 5B. When we prepared a prototype Fig. 5B after obtaining data for lanes 1-6, and before obtaining data for lanes 7-10 in repeated experiments, we used portions of lanes 1-6 as tentative lanes 7-10. Then using new data obtained, we had Fig. 5B. Regrettably, when I made the composite Figure 5 for submission, I most probably used the wrong prototype Fig. 5B instead of the true one. I will ask Dr Higashitsuji to find the original data. If no luck, I will consult the editor how to deal with this. Regards, Jun , 
 Dear Lucinisca, A correction indicating that there was an error in Fig 5B will be published in JBC. ![file] Since lanes 7 to 10 did not show u200bthe experimental data obtained, these lanes are removed. This correction does not affect the results or conclusions of this work. The authors sincerely apologize for the mistake u200bthat occurred during figure preparation and for any inconvenience this u200berror may have caused readers. Sincerely, Jun , 
 2020 correction. https: www.jbc.org content 295 27 9264.short There was an error in Fig. 5B. Lanes 7u201310 did not show the experimental data obtained. This error has now been corrected by removing these lanes. Accordingly, the legend and the text referring to Fig. 5B should be changed from u201cTSA or nicotinamideu201d to u201cTSAu201d and from u201cbut not nicotinamideu201d to u201cbut not nicotinamide (data not shown),u201d respectively. This correction does not affect the results or conclusions of this work. The authors sincerely apologize for the mistake that occurred during figure preparation and for any inconvenience this error may have caused readers. ,