PMID- 33916919
OWN - NLM
STAT- MEDLINE
DCOM- 20210520
LR  - 20210520
IS  - 1422-0067 (Electronic)
IS  - 1422-0067 (Linking)
VI  - 22
IP  - 8
DP  - 2021 Apr 7
TI  - Evidence for a Negative Correlation between Human Reactive Enamine-Imine 
      Intermediate Deaminase A (RIDA) Activity and Cell Proliferation Rate: Role of 
      Lysine Succinylation of RIDA.
LID - 10.3390/ijms22083804 [doi]
LID - 3804
AB  - Reactive intermediate deaminase (Rid) proteins are enzymes conserved in all 
      domains of life. UK114, a mammalian member of RidA subfamily, has been firstly 
      identified as a component of liver perchloric acid-soluble proteins (L-PSP). 
      Although still poorly defined, several functions have been attributed to the 
      mammalian protein UK114/RIDA, including the reactive intermediate deamination 
      activity. The expression of UK114/RIDA has been observed in some tumors, arousing 
      interest in this protein as an evaluable tumor marker. However, other studies 
      reported a negative correlation between UK114/RIDA expression, tumor 
      differentiation degree and cell proliferation. This work addressed the question 
      of UK114/RIDA expression in human non-tumor HEK293 cell lines and in some human 
      tumor cell lines. Here we reported that human RIDA (hRIDA) was expressed in all 
      the analyzed cell line and subjected to lysine (K-)succinylation. In HEK293, 
      hRIDA K-succinylation was negatively correlated to the cell proliferation rate 
      and was under the control of SIRT5. Moreover, K-succinylation clearly altered 
      hRIDA quantification by immunoblotting, explaining, at least in part, some 
      discrepancies about RIDA expression reported in previous studies. We found that 
      hRIDA was able to deaminate reactive enamine-imine intermediates and that 
      K-succinylation drastically reduced deaminase activity. As predicted by in silico 
      analysis, the observed reduction of deaminase activity has been related to the 
      drastic alterations of hRIDA structure inferred by K-succinylation. The role of 
      hRIDA and the importance of its K-succinylation in cell metabolism, especially in 
      cancer biology, have been discussed.
FAU - Siculella, Luisa
AU  - Siculella L
AUID- ORCID: 0000-0002-6890-3674
AD  - Laboratory of Molecular Biology, Department of Biological and Environmental 
      Sciences and Technologies, University of Salento, 73100 Lecce, Italy.
FAU - Giannotti, Laura
AU  - Giannotti L
AD  - Laboratory of Molecular Biology, Department of Biological and Environmental 
      Sciences and Technologies, University of Salento, 73100 Lecce, Italy.
FAU - Di Chiara Stanca, Benedetta
AU  - Di Chiara Stanca B
AD  - Laboratory of Molecular Biology, Department of Biological and Environmental 
      Sciences and Technologies, University of Salento, 73100 Lecce, Italy.
FAU - Calcagnile, Matteo
AU  - Calcagnile M
AUID- ORCID: 0000-0001-9745-4583
AD  - Laboratory of Microbiology, Department of Biological and Environmental Sciences 
      and Technologies, University of Salento, 73100 Lecce, Italy.
FAU - Rochira, Alessio
AU  - Rochira A
AD  - Laboratory of Molecular Biology, Department of Biological and Environmental 
      Sciences and Technologies, University of Salento, 73100 Lecce, Italy.
FAU - Stanca, Eleonora
AU  - Stanca E
AD  - Laboratory of Molecular Biology, Department of Biological and Environmental 
      Sciences and Technologies, University of Salento, 73100 Lecce, Italy.
FAU - Alifano, Pietro
AU  - Alifano P
AD  - Laboratory of Microbiology, Department of Biological and Environmental Sciences 
      and Technologies, University of Salento, 73100 Lecce, Italy.
FAU - Damiano, Fabrizio
AU  - Damiano F
AUID- ORCID: 0000-0001-7828-9519
AD  - Laboratory of Molecular Biology, Department of Biological and Environmental 
      Sciences and Technologies, University of Salento, 73100 Lecce, Italy.
LA  - eng
PT  - Journal Article
DEP - 20210407
PL  - Switzerland
TA  - Int J Mol Sci
JT  - International journal of molecular sciences
JID - 101092791
RN  - 0 (Heat-Shock Proteins)
RN  - EC 3.1.- (Ribonucleases)
RN  - EC 3.5.1.- (SIRT5 protein, human)
RN  - EC 3.5.1.- (Sirtuins)
RN  - EC 3.5.99.10 (RIDA protein, human)
RN  - K3Z4F929H6 (Lysine)
SB  - IM
MH  - Cell Line
MH  - Cell Proliferation/*physiology
MH  - Enzyme Activation
MH  - Gene Expression
MH  - Heat-Shock Proteins/chemistry/genetics/*metabolism
MH  - Humans
MH  - Lysine/metabolism
MH  - Models, Molecular
MH  - Protein Conformation
MH  - Protein Processing, Post-Translational
MH  - Ribonucleases/chemistry/genetics/*metabolism
MH  - Sirtuins/metabolism
MH  - Structure-Activity Relationship
PMC - PMC8067581
OTO - NOTNLM
OT  - 3D protein modeling
OT  - L-PSP
OT  - YigF/YER057c/UK114
OT  - cancer proliferation
OT  - lysine succinylation
OT  - metabolic sensor
OT  - reactive imine/enamine intermediate deaminase A
COIS- The authors declare no conflict of interest.
EDAT- 2021/05/01 06:00
MHDA- 2021/05/21 06:00
PMCR- 2021/04/07
CRDT- 2021/04/30 01:04
PHST- 2021/02/24 00:00 [received]
PHST- 2021/03/29 00:00 [revised]
PHST- 2021/04/02 00:00 [accepted]
PHST- 2021/04/30 01:04 [entrez]
PHST- 2021/05/01 06:00 [pubmed]
PHST- 2021/05/21 06:00 [medline]
PHST- 2021/04/07 00:00 [pmc-release]
AID - ijms22083804 [pii]
AID - ijms-22-03804 [pii]
AID - 10.3390/ijms22083804 [doi]
PST - epublish
SO  - Int J Mol Sci. 2021 Apr 7;22(8):3804. doi: 10.3390/ijms22083804.