PMID- 38001686
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20240210
IS  - 2072-6694 (Print)
IS  - 2072-6694 (Electronic)
IS  - 2072-6694 (Linking)
VI  - 15
IP  - 22
DP  - 2023 Nov 15
TI  - ASPP2 Is Phosphorylated by CDK1 during Mitosis and Required for Pancreatic Cancer 
      Cell Proliferation.
LID - 10.3390/cancers15225424 [doi]
LID - 5424
AB  - (1) Background: pancreatic cancer is highly lethal. The role of 
      apoptosis-stimulating protein of p53-2 (ASPP2) in this lethal disease remains 
      unclear. This protein belongs to the ASPP family of p53 interacting proteins. 
      Previous studies in this lab used phosphate-binding tag (Phos-tag) sodium dodecyl 
      sulfate (SDS) polyacrylamide gels and identified a motility upshift of the ASPP 
      family of proteins during mitosis. (2) Purpose: this study expands on previous 
      findings to identify the detailed phosphorylation regulation of ASPP2 during 
      mitosis, as well as the function of ASPP2 in pancreatic cancer. (3) Methods: the 
      Phos-tag technique was used to investigate the phosphorylation mechanism of ASPP2 
      during mitosis. Phospho-specific antibodies were generated to validate the 
      phosphorylation of ASPP2, and ASPP2-inducible expression cell lines were 
      established to determine the role of ASPP2 in pancreatic cancer. RNA sequencing 
      (RNA-Seq) was used to uncover the downstream targets of ASPP2. (4) Results: 
      results demonstrate that ASPP2 is phosphorylated during mitosis by 
      cyclin-dependent kinase 1 (CDK1) at sites S562 and S704. In vitro and in vivo 
      results show that ASPP2 is required for pancreatic cancer growth. Furthermore, 
      the expressions of yes-associated protein (YAP)-related genes are found to be 
      dramatically altered by ASPP2 depletion. Together, these findings reveal the 
      phosphorylation mechanism of ASPP2 during mitosis. Collectively, results strongly 
      indicate that ASPP2 is a potential target for abating tumor cell growth in 
      pancreatic cancer.
FAU - Xiao, Yi
AU  - Xiao Y
AUID- ORCID: 0000-0002-1389-3106
AD  - Eppley Institute for Research in Cancer and Allied Diseases, Fred & Pamela 
      Buffett Cancer Center, University of Nebraska Medical Center, Omaha, NE 68198, 
      USA.
FAU - Chen, Yuanhong
AU  - Chen Y
AD  - Eppley Institute for Research in Cancer and Allied Diseases, Fred & Pamela 
      Buffett Cancer Center, University of Nebraska Medical Center, Omaha, NE 68198, 
      USA.
FAU - Chen, Jianan
AU  - Chen J
AD  - Eppley Institute for Research in Cancer and Allied Diseases, Fred & Pamela 
      Buffett Cancer Center, University of Nebraska Medical Center, Omaha, NE 68198, 
      USA.
FAU - Dong, Jixin
AU  - Dong J
AUID- ORCID: 0000-0002-2757-4464
AD  - Eppley Institute for Research in Cancer and Allied Diseases, Fred & Pamela 
      Buffett Cancer Center, University of Nebraska Medical Center, Omaha, NE 68198, 
      USA.
LA  - eng
GR  - P30 CA036727/CA/NCI NIH HHS/United States
GR  - R01 CA273226/CA/NCI NIH HHS/United States
GR  - U54 CA274329/CA/NCI NIH HHS/United States
GR  - U54 CA274329/NH/NIH HHS/United States
PT  - Journal Article
DEP - 20231115
PL  - Switzerland
TA  - Cancers (Basel)
JT  - Cancers
JID - 101526829
PMC - PMC10670399
OTO - NOTNLM
OT  - ASPP2
OT  - CDK1
OT  - YAP
OT  - mitosis
OT  - p53
OT  - pancreatic cancer
OT  - phosphorylation
COIS- The authors declare no conflict of interest.
EDAT- 2023/11/25 12:46
MHDA- 2023/11/25 12:47
PMCR- 2023/11/15
CRDT- 2023/11/25 01:06
PHST- 2023/09/28 00:00 [received]
PHST- 2023/11/10 00:00 [revised]
PHST- 2023/11/13 00:00 [accepted]
PHST- 2023/11/25 12:47 [medline]
PHST- 2023/11/25 12:46 [pubmed]
PHST- 2023/11/25 01:06 [entrez]
PHST- 2023/11/15 00:00 [pmc-release]
AID - cancers15225424 [pii]
AID - cancers-15-05424 [pii]
AID - 10.3390/cancers15225424 [doi]
PST - epublish
SO  - Cancers (Basel). 2023 Nov 15;15(22):5424. doi: 10.3390/cancers15225424.