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pmid:29795372

FAM188B enhances cell survival via interaction with USP7.

Eun-Seok Choi · Hanna Lee · Jee Young Sung · Chang-Hun Lee · Hyonchol Jang · Kyung Tae Kim · Yong-Nyun Kim · Hyoung-Pyo Kim · Sung-Ho Goh

Cell death & disease · 2018 doi:10.1038/s41419-018-0650-6

Paper

complete

Experiment

complete

Data

partial

Analysis

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absent

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Record details sci_version · id · kind · revision · content_hash · schema · created_at · updated_at · generator
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pmid:29795372
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paper object · 10 fields
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title
FAM188B enhances cell survival via interaction with USP7.
doi
10.1038/s41419-018-0650-6
pmid
29795372
authors array · 9 items
[0]
Eun-Seok Choi
[1]
Hanna Lee
[2]
Jee Young Sung
[3]
Chang-Hun Lee
[4]
Hyonchol Jang
[5]
Kyung Tae Kim
[6]
Yong-Nyun Kim
[7]
Hyoung-Pyo Kim
[8]
Sung-Ho Goh
journal
Cell death & disease
year
2018
abstract
We have previously reported that FAM188B showed significant differential exon usage in cancers (NCBI GEO GSE30727), but the expression and function of FAM188B is not well characterized. In the present study, we explored the functions of FAM188B by a knockdown strategy, using siRNAs specific for FAM188B in colon cancer cell lines. FAM188B is a novel gene that encodes a protein that is evolutionarily conserved among mammals. Its mRNA has been found to be highly expressed in most solid tumors, including colorectal cancer. FAM188B knockdown induced cell growth inhibition due to an increase in apoptosis in colon cancer cell lines. Interestingly, siFAM188B treatment induced the upregulation and activation of p53, and consequently increased p53-regulated pro-apoptotic proteins, PUMA and BAX. Proteomic analysis of FAM188B immunocomplexes revealed p53 and USP7 as putative FAM188B-interacting proteins. Deletion of the putative USP7-binding motif in FAM188B reduced complex formation of FAM188B with USP7. It is noteworthy that FAM188B knockdown resulted in a decrease in overall ubiquitination in the p53 immunocomplexes, as well as p53 ubiquitination, because USP7 is involved in p53 deubiquitination. FAM188B knockdown inhibited both colony formation and anchorage-independent growth in vitro. In addition, FAM188B knockdown by siRNA reduced tumor growth in xenografted mice, with an increase in p53 proteins. Taken together, our data suggest that FAM188B is a putative oncogene that functions via interaction with USP7. Therefore, control of FAM188B could be a possible target to inhibit tumor growth.
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Mutated KRAS induces overexpression of DUSP4, a MAP-kinase phosphatase, and SMYD3, a histone methyltransferase, in rectal carcinomas
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y, we explored the functions of FAM188B by a knockdown strategy, using siRNAs specific for FAM188B
[1]
tumors, including colorectal cancer. FAM188B knockdown induced cell growth inhibition due to an inc
[2]
88B with USP7. It is noteworthy that FAM188B knockdown resulted in a decrease in overall ubiquitina
[3]
is involved in p53 deubiquitination. FAM188B knockdown inhibited both colony formation and anchorag
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cell growth inhibition due to an increase in apoptosis in colon cancer cell lines. Interestingly, s
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Materials and methods In vivo analysis of FAM188B silencing HCT-116 (2.0 ×
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The statistical significance of differences between groups was determined using χ2-test and Student’s t-test. p-values <0.05 were considered statistically significant.
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Complete file
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In the present study, we explored the functions of FAM188B by a knockdown strategy, using siRNAs specific for FAM188B in colon cancer cell lines. FAM188B is a novel gene that encodes a protein that is evolutionarily conserved among mammals. Its mRNA has been found to be highly expressed in most solid tumors, including colorectal cancer. FAM188B knockdown induced cell growth inhibition due to an increase in apoptosis in colon cancer cell lines. Interestingly, siFAM188B treatment induced the upregulation and activation of p53, and consequently increased p53-regulated pro-apoptotic proteins, PUMA and BAX. Proteomic analysis of FAM188B immunocomplexes revealed p53 and USP7 as putative FAM188B-interacting proteins. Deletion of the putative USP7-binding motif in FAM188B reduced complex formation of FAM188B with USP7. It is noteworthy that FAM188B knockdown resulted in a decrease in overall ubiquitination in the p53 immunocomplexes, as well as p53 ubiquitination, because USP7 is involved in p53 deubiquitination. FAM188B knockdown inhibited both colony formation and anchorage-independent growth in vitro. In addition, FAM188B knockdown by siRNA reduced tumor growth in xenografted mice, with an increase in p53 proteins. Taken together, our data suggest that FAM188B is a putative oncogene that functions via interaction with USP7. 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