hSSB1 binds and protects p21 from ubiquitin-mediated degradation and positively correlates with p21 in human hepatocellular carcinomas

Xu, Shihe; Feng, Zizhen; Zhang, M.; Wu, Yifan; Sang, Yi; Xu, Hongde; Lv, Xiaobin; Hu, Kunpeng; Jie, Cao; Zhang, Rong; Chen, Likun; Liu, Mengzhong; Yun, Jie; Zeng, Yi‐Xin; Kang, Tiebang

doi:10.1038/onc.2010.596

Cited by 56 publications

(67 citation statements)

References 43 publications

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“…First, we tested whether the regulation of p53 by hSSB1 is involved in the G1/S transition. As shown in Supplementary information, Figure S3, the promotion of the G1/S transition by hSSB1 knockdown was mostly rescued by overexpression of p21, but neither p53 nor p300, in HepG2 cells, indicating that the G1/S transition regulated by hSSB1 is directly through p21 protein, consistent with our recent report [28]. Second, we tested whether hSSB1 affects apoptosis induced by doxorubicin.…”

Section: Hssb1 Is Involved In the P53-dependent G2/m Checkpoint In Resupporting

confidence: 72%

“…Much evidence has been presented showing that both p53 and p21 participate in arrest at the G1/S and G2/M checkpoints after DNA damage [47][48][49][50]. Our results show that hSSB1 is required to stabilize both p53 and p21 in response to IR ( Figure 5A) [28], and that hSSB1 knockdown allows bypass of the G2/M checkpoint response to IR. The effects of hSSB1 knockdown were mostly rescued by overexpressing p21 [28], and mildly by overexpressing p53 or p300 in cells ( Figure 5E).…”

Section: Discussionmentioning

confidence: 52%

“…We have recently revealed that hSSB1 binds p21 and modulates its degradation in both p53 wild-type and p53-deficient cell lines to regulate cell cycle and DNA damage checkpoint [28]. In current study, when hSSB1 was depleted, p21 was decreased at both the mRNA and protein levels in p53 wild-type cancer cell lines such as HepG2, SMMC-7721 and Bel7402 ( Figure 1A), whereas in the p53-null Hep3B cells, the p21 mRNA level remained constant while the protein level was downregulated ( Figure 1A).…”

Section: Discussionmentioning

confidence: 99%

“…We have recently shown that p21 protein was markedly reduced in multiple cancer cell lines when hSSB1 was knocked down [28]. However, the regulation of p21 by hSSB1 is different among those cell lines.…”

Section: Rnai-mediated Depletion Of Hssb1 Reduces the Protein Levels mentioning

confidence: 99%

“…Mechanistically, hSSB1 has recently been shown to (1) be required for the efficient recruitment of the MRN complex, (2) bind directly with NBS1 and (3) stimulate the endonuclease activity of the MRN complex [26,27]. Moreover, we have recently shown that hSSB1 regulates cell cycle progression and DNA damage checkpoints by modulating the stability of p21 in cancer cells [28]. In this study, we report that hSSB1 not only physically interacts with p53 and affects its stability, but also associates with the acetyltransferase p300 to regulate the acetylation of p53 at lysine 382, a key event for the p53-mediated expression of p21.…”

Section: Introductionmentioning

confidence: 99%

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hSSB1 regulates both the stability and the transcriptional activity of p53

Chen

et al. 2012

Cell Res

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The tumor suppressor p53 is essential for several cellular processes that are involved in the response to diverse genotoxic stress, including cell cycle arrest, DNA repair, apoptosis and senescence. Studies of the regulation of p53 have mostly focused on its stability and transactivation; however, new regulatory molecules for p53 have also been frequently identified. Here, we report that human ssDNA binding protein SSB1 (hSSB1), a novel DNA damageassociated protein, can interact with p53 and protect p53 from ubiquitin-mediated degradation. Furthermore, hSSB1 also associates with the acetyltransferase p300 and is required for efficient transcriptional activation of the p53 target gene p21 by affecting the acetylation of p53 at lysine382. Functionally, the hSSB1 knockdown-induced abrogation of the G2/M checkpoint is partially dependent on p53 or p300. Collectively, our results indicate that hSSB1 may regulate DNA damage checkpoints by positively modulating p53 and its downstream target p21.

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Section: Hssb1 Is Involved In the P53-dependent G2/m Checkpoint In Resupporting

confidence: 72%

Section: Discussionmentioning

confidence: 52%

Section: Discussionmentioning

confidence: 99%

Section: Rnai-mediated Depletion Of Hssb1 Reduces the Protein Levels mentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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hSSB1 regulates both the stability and the transcriptional activity of p53

Chen

et al. 2012

Cell Res

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Down‐regulation of prostate stem cell antigen (PSCA) by Slug promotes metastasis in nasopharyngeal carcinoma

Wang

Sang

Tang

et al. 2015

The Journal of Pathology

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Distant metastasis and local recurrence are still the major causes for failure of treatment in patients with nasopharyngeal carcinoma (NPC), making it urgent to further elicit the molecular mechanisms of NPC metastasis. Using a gene microarray including transcription factors and known markers for cancer stem cells, prostate stem cell antigen (PSCA) was found to be significantly down-regulated in metastatic NPC in lymph node, compared to its primary tumour, and in NPC cell lines with high metastatic ability compared to those with low metastatic ability. NPC patients with low PSCA expression had a consistently poor metastasis-free survival (p = 0.003). Knockdown and overexpression of PSCA respectively enhanced and impaired the migration and invasion in vitro and the lung metastasis in vivo of NPC cells. Mechanistically, the enhancement of NPC metastasis by knocking down PSCA probably involved epithelial-mesenchymal transition (EMT), by up-regulating N-cadherin and ZEB1/2 and by activating RhoA. The down-regulation of PSCA in NPC cells resulted directly from the binding of Slug to the PSCA promoter. PSCA may be a potential diagnostic marker and therapeutic target for patients with NPC.

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DNA‐dependent phase separation by human SSB2 (NABP1/OBFC2A) protein points to adaptations to eukaryotic genome repair processes

Kovács,

Harami,

Pálinkás

et al. 2024

Protein Science

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Single‐stranded DNA binding proteins (SSBs) are ubiquitous across all domains of life and play essential roles via stabilizing and protecting single‐stranded (ss) DNA as well as organizing multiprotein complexes during DNA replication, recombination, and repair. Two mammalian SSB paralogs (hSSB1 and hSSB2 in humans) were recently identified and shown to be involved in various genome maintenance processes. Following our recent discovery of the liquid–liquid phase separation (LLPS) propensity of Escherichia coli (Ec) SSB, here we show that hSSB2 also forms LLPS condensates under physiologically relevant ionic conditions. Similar to that seen for EcSSB, we demonstrate the essential contribution of hSSB2's C‐terminal intrinsically disordered region (IDR) to condensate formation, and the selective enrichment of various genome metabolic proteins in hSSB2 condensates. However, in contrast to EcSSB‐driven LLPS that is inhibited by ssDNA binding, hSSB2 phase separation requires single‐stranded nucleic acid binding, and is especially facilitated by ssDNA. Our results reveal an evolutionarily conserved role for SSB‐mediated LLPS in the spatiotemporal organization of genome maintenance complexes. At the same time, differential LLPS features of EcSSB and hSSB2 point to functional adaptations to prokaryotic versus eukaryotic genome metabolic contexts.

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hSSB1 binds and protects p21 from ubiquitin-mediated degradation and positively correlates with p21 in human hepatocellular carcinomas

Cited by 56 publications

References 43 publications

hSSB1 regulates both the stability and the transcriptional activity of p53

hSSB1 regulates both the stability and the transcriptional activity of p53

Down‐regulation of prostate stem cell antigen (PSCA) by Slug promotes metastasis in nasopharyngeal carcinoma

DNA‐dependent phase separation by human SSB2 (NABP1/OBFC2A) protein points to adaptations to eukaryotic genome repair processes

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