Truncated PARP1 mediates ADP-ribosylation of RNA polymerase III for apoptosis

Chen, Qian; Ma, Kai; Li, Xiuhua; Chen, Shih-Hsun; Yu, Yonghao; Leung, Anthony Kwan; Yu, Xiaochun

doi:10.1038/s41421-021-00355-1

Cited by 24 publications

(18 citation statements)

References 69 publications

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“…But PARP1 induces cell death for genome integrity in the case of extensive damage [17]. With the research goes further, PARP1 is reported be involved in many cellular processes such as cell apoptosis [18,23], chromatin remodeling [38] and gene expression [20,39]. PARP1 is also involved in malignant tumors development and resistance of cancers [40][41][42][43][44], and it is regarded as a potential therapeutic target in certain leukemia [24,45].…”

Section: Discussionmentioning

confidence: 99%

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The role of E3 ubiquitin ligase WWP2 and the regulation of PARP1 by ubiquitinated degradation in acute lymphoblastic leukemia

Huang

et al. 2022

Cell Death Discov.

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Acute lymphoblastic leukemia (ALL) has been a huge threat for people's health and finding effective target therapy is urgent and important. WWP2, as one of E3 ubiquitin ligase, is involved in many biological processes by specifically binding to substrates. PARP1 plays a role in cell apoptosis and is considered as a therapeutic target of certain cancers. In this study, we firstly found that WWP2 expressed higher in newly diagnosed ALL patients comparing with complete remission (CR) ALL patients and normal control people, and WWP2 in relapse ALL patients expressed higher than normal control people. WWP2 expression was related with the FAB subtype of ALL and the proportion of blast cells in bone marrow blood tested by flow cytometry. We demonstrated knockout WWP2 inhibited the ALL growth and enhanced apoptosis induced by Dox in vitro and vivo for the first time. WWP2 negatively regulated and interacted with PARP1 and WWP2 mechanically degraded PARP1 through polyubiquitin-proteasome pathway in ALL. These findings suggested WWP2 played a role in ALL development as well as growth and apoptosis, and also displayed a regulatory pathway of PARP1, which provided a new potential therapeutic target for the treatment of ALL.

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Section: Discussionmentioning

confidence: 99%

“…Poly (ADP-ribose) polymerase 1 (PARP1) is the founding member of PARP family [16,17], which participates in DNA repair and gene integrity [18][19][20]. And excessive activation of PARP1 induced by oxidative stress leads to the depletion of ATP, which causes cell apoptosis [21].…”

Section: Introductionmentioning

confidence: 99%

The role of E3 ubiquitin ligase WWP2 and the regulation of PARP1 by ubiquitinated degradation in acute lymphoblastic leukemia

Huang

et al. 2022

Cell Death Discov.

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“…In the apoptotic vesicle caspase 9 is activated, with further activation of caspase 3 and 7, leading to apoptosis ( 29 – 31 ). During apoptosis, caspase 3 cleaves PARP1, and the increase of cleaved PARP1 hinders DNA damage repair and further promotes apoptosis ( 32 ). Normally, p21 binds to CDKs to block CDK protein activity causing cell cycle arrest ( 33 ).…”

Section: Discussionmentioning

confidence: 99%

HRK inhibits colorectal cancer cells proliferation by suppressing the PI3K/AKT/mTOR pathway

et al. 2022

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BackgroundAs one of the most common malignant tumor, colorectal cancer (CRC) continues to have a high incidence and mortality rate. HRK belongs to the BCL-2 protein family, which has been shown to have antitumor effects in prostate cancer. However, its role in colorectal cancer is not yet known.MethodsIn this study, we verified the expression levels of HRK in colorectal cancer tissues by public database search as well as immunohistochemistry. Next, we analyzed HRK expression levels in CRC tissues,adjacent non-cancerous tissues, cell lines and normal intestinal epithelial cells by qPCR and Western blotting. CCK-8 proliferation assays, transwell assays, wound healing assays, colony assays and flow cytometry were performed to clarified the effect of HRK on CRC cells. Western blotting and rescue experiments were used to determine the role of HRK in regulating PI3K/AKT/mTOR signaling pathway.ResultsHRK expression was lower in CRC tissues and cell lines. Gain and loss of function experiments showed that HRK decreased proliferation, invasion and migration of CRC cells. Low expression of HRK inhibited CRC cell apoptosis as well as activated the PI3K/AKT/mTOR signaling pathway. In addition, rapamycin inhibits the activation of PI3K/AKT/mTOR signaling pathway and reverses HRK-induced alterations in cell biological functions.ConclusionOur study demonstrates that HRK is lowly expressed in colorectal cancer tissues. And for the first time, HRK was shown to promote apoptosis and inhibit proliferation of colorectal cancer cells by inhibiting PI3K/AKT/mTOR signaling pathway. HRK represents a potential target for the treatment of CRC.

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“…This indicates that PARP1 also negatively regulates TMEJ through Polθ PARylation to maintain appropriate activity of the TMEJ pathway. RNA polymerase III is a binding partner of truncated PARP1, and three subunits (POLR3B, POLR3F, and POLR3G) can be ADP-ribosylated during cytosolic DNA-induced apoptosis (Chen et al, 2022). In addition, PARP1 inhibits elongation of RNA polymerase II via suppressing the transcription elongation factor P-TEFb.…”

Section: Enzymes Involved In Nucleic Acid Processingmentioning

confidence: 99%

Human PARP1 substrates and regulators of its catalytic activity: An updated overview

et al. 2023

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Poly (ADP-ribose) polymerase 1 (PARP1) is a key DNA damage sensor that is recruited to damaged sites after DNA strand breaks to initiate DNA repair. This is achieved by catalyzing attachment of ADP-ribose moieties, which are donated from NAD+, on the amino acid residues of itself or other acceptor proteins. PARP inhibitors (PARPi) that inhibit PARP catalytic activity and induce PARP trapping are commonly used for treating BRCA1/2-deficient breast and ovarian cancers through synergistic lethality. Unfortunately, resistance to PARPi frequently occurs. In this review, we present the novel substrates and regulators of the PARP1-catalyzed poly (ADP-ribosyl)ation (PARylatison) that have been identified in the last 3 years. The overall aim is the presentation of protein interactions of potential therapeutic intervention for overcoming the resistance to PARPi.

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Truncated PARP1 mediates ADP-ribosylation of RNA polymerase III for apoptosis

Cited by 24 publications

References 69 publications

The role of E3 ubiquitin ligase WWP2 and the regulation of PARP1 by ubiquitinated degradation in acute lymphoblastic leukemia

The role of E3 ubiquitin ligase WWP2 and the regulation of PARP1 by ubiquitinated degradation in acute lymphoblastic leukemia

HRK inhibits colorectal cancer cells proliferation by suppressing the PI3K/AKT/mTOR pathway

Human PARP1 substrates and regulators of its catalytic activity: An updated overview

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