PMID- 31652443
OWN - NLM
STAT- MEDLINE
DCOM- 20200915
LR  - 20200915
IS  - 1573-4935 (Electronic)
IS  - 0144-8463 (Print)
IS  - 0144-8463 (Linking)
VI  - 39
IP  - 10
DP  - 2019 Oct 30
TI  - Wild-type menin is rapidly degraded via the ubiquitin-proteasome pathway in a rat 
      insulinoma cell line.
LID - 10.1042/BSR20190471 [doi]
LID - BSR20190471
AB  - Menin is encoded by multiple endocrine neoplasia type 1 (MEN1) gene, the germ 
      line mutations of which are the main cause of pancreatic neuroendocrine tumors 
      (PNETs). To date, a large number of frameshift, nonsense and missense mutations 
      of MEN1 have been identified to be responsible for part of MEN1-defficient PNETs 
      patients due to truncation or rapid degradation of menin protein. However, the 
      stability of the wild-type (WT) menin in PNETs is totally unknown. In the present 
      study, we observed ubiquitination of WT menin in 293T cells by transfection of 
      ectopic WT menin and HA-ubiquitin. As expected, either endogenous or ectopic WT 
      menin is stable in 293T cells, whereas in INS-1 cells, a rat insulinoma cell line 
      derived from PNETs, either endogenous or ectopic WT menin is rapidly degraded 
      through ubiquitin-proteasome pathway. Furthermore, the degradation of WT menin is 
      more rapid in the presence of serum. Our findings suggest that in part of PNETs 
      patients with WT MEN1, a ubiquitin-proteasome system targeting menin is untimely 
      activated.
CI  - (c) 2019 The Author(s).
FAU - Jiang, Zongzhe
AU  - Jiang Z
AD  - Experimental Medicine Center, The Affiliated Hospital of Southwest Medical 
      University, Luzhou 646000, Sichuan, China.
FAU - Wan, Shengrong
AU  - Wan S
AD  - Endocrinology Department, The Affiliated Hospital of Southwest Medical 
      University, Luzhou 646000, Sichuan, China.
FAU - Xing, Bowen
AU  - Xing B
AD  - Diabetes Research Center, School of Medicine, Shenzhen University, Shenzhen 
      518060, Guangdong, China.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - England
TA  - Biosci Rep
JT  - Bioscience reports
JID - 8102797
RN  - 0 (Men1 protein, rat)
RN  - 0 (Neoplasm Proteins)
RN  - 0 (Transcription Factors)
RN  - 0 (Ubiquitin)
RN  - EC 3.4.25.1 (Proteasome Endopeptidase Complex)
SB  - IM
MH  - Animals
MH  - Insulinoma/genetics/*metabolism/pathology
MH  - Neoplasm Proteins/genetics/*metabolism
MH  - Pancreatic Neoplasms/genetics/*metabolism/pathology
MH  - Proteasome Endopeptidase Complex/genetics/*metabolism
MH  - *Proteolysis
MH  - Rats
MH  - Transcription Factors/genetics/*metabolism
MH  - Ubiquitin/genetics/*metabolism
PMC - PMC6822493
OTO - NOTNLM
OT  - INS-1 cell
OT  - Insulinoma
OT  - Menin
OT  - Ubiquitin-proteasome
COIS- The authors declare that there are no competing interests associated with the 
      manuscript.
EDAT- 2019/10/28 06:00
MHDA- 2020/09/17 06:00
PMCR- 2019/10/18
CRDT- 2019/10/26 06:00
PHST- 2019/02/25 00:00 [received]
PHST- 2019/09/18 00:00 [revised]
PHST- 2019/10/02 00:00 [accepted]
PHST- 2019/10/26 06:00 [entrez]
PHST- 2019/10/28 06:00 [pubmed]
PHST- 2020/09/17 06:00 [medline]
PHST- 2019/10/18 00:00 [pmc-release]
AID - 220725 [pii]
AID - BSR20190471 [pii]
AID - 10.1042/BSR20190471 [doi]
PST - ppublish
SO  - Biosci Rep. 2019 Oct 30;39(10):BSR20190471. doi: 10.1042/BSR20190471.