PMID- 36575252
OWN - NLM
STAT- MEDLINE
DCOM- 20230824
LR  - 20230824
IS  - 1432-0878 (Electronic)
IS  - 0302-766X (Linking)
VI  - 392
IP  - 2
DP  - 2023 May
TI  - STUB1 directs FOXQ1-mediated transactivation of Ldha gene and facilitates lactate 
      production in mouse Sertoli cells.
PG  - 565-579
LID - 10.1007/s00441-022-03705-x [doi]
AB  - Sertoli cells (SCs) preferentially use glucose to convert to lactate. As an 
      energy source, lactate is essential for survival of developed germ cells (GCs) 
      due to its anti-apoptotic effect. Failure to maintain lactate metabolism 
      homeostasis leads to infertility or germ cell apoptosis. Several Sertoli 
      cell-expressed genes, such as Foxq1 and Gata4, have been identified as critical 
      regulators for lactate synthesis, but the pathways that potentially modulate 
      their expression remain ill defined. Although recent work from our collaborators 
      pointed to an involvement of STIP1 homology and U-box-containing protein 1 
      (STUB1) in the modulation of Sertoli cell response to GCs-derived IL-1alpha, a true 
      physiological function of STUB1 signaling in SCs has not been demonstrated. We 
      therefore conditionally ablated Stub1 in SCs using Amh-Cre. Stub1 knockout males 
      exhibited impaired fertility due to oligozoospermia and asthenospermia, possibly 
      caused by lactate deficiency. Furthermore, by means of chromatin 
      immunoprecipitation, in vivo ubiquitination, and luciferase reporter assays, we 
      showed that STUB1 directed forkhead box Q1 (FOXQ1)-mediated transactivation of 
      the lactate dehydrogenase A (Ldha) gene via K63-linked non-proteolytic 
      polyubiquitination, thus facilitating lactate production in follicle-stimulating 
      hormone (FSH)-stimulated SCs. In agreement, overexpression of LDHA by lentivirus 
      infection effectively rescued the lactate production in TM4(Stub1-/-) cells. Our 
      results collectively identify STUB1-mediated transactivation of FOXQ1 signaling 
      as a post-translationally modified transcriptional regulatory network underlying 
      nursery function in SCs, which may nutritionally contribute to Sertoli cell 
      dysfunction of male infertility.
CI  - (c) 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, 
      part of Springer Nature.
FAU - Yang, Yang
AU  - Yang Y
AD  - Department of Gynecology and Obstetrics, the First Affiliated Hospital of Xi'an 
      Jiaotong University, No. 277 West Yanta Road, Xi'an 710061, Shaanxi, People's 
      Republic of China.
AD  - Reproductive Medicine Center, Xi'an People's Hospital (Xi'an NO.4 Hospital), 
      710004, Shaanxi, People's Republic of China.
FAU - Ma, Yuan
AU  - Ma Y
AD  - Reproductive Medicine Center, Department of Obstetrics and Gynecology, Tangdu 
      Hospital, Air Force Medical University, Xi'an 710038, Shaanxi, People's Republic 
      of China.
FAU - Li, Mao
AU  - Li M
AD  - Reproductive Medicine Center, Department of Obstetrics and Gynecology, Tangdu 
      Hospital, Air Force Medical University, Xi'an 710038, Shaanxi, People's Republic 
      of China.
FAU - Zhu, Hongli
AU  - Zhu H
AD  - Reproductive Medicine Center, Xi'an People's Hospital (Xi'an NO.4 Hospital), 
      710004, Shaanxi, People's Republic of China.
FAU - Shi, Panpan
AU  - Shi P
AD  - Reproductive Medicine Center, Xi'an People's Hospital (Xi'an NO.4 Hospital), 
      710004, Shaanxi, People's Republic of China.
FAU - An, Ruifang
AU  - An R
AUID- ORCID: 0000-0002-4381-9679
AD  - Department of Gynecology and Obstetrics, the First Affiliated Hospital of Xi'an 
      Jiaotong University, No. 277 West Yanta Road, Xi'an 710061, Shaanxi, People's 
      Republic of China. xyfyfk01@163.com.
LA  - eng
GR  - 81901510/Major Research Plan/
GR  - NO.: D-9/Research Incubation Fund of Xi'an People's Hospital/
PT  - Journal Article
DEP - 20221228
PL  - Germany
TA  - Cell Tissue Res
JT  - Cell and tissue research
JID - 0417625
RN  - 33X04XA5AT (Lactic Acid)
RN  - 0 (Foxq1 protein, mouse)
RN  - EC 2.3.2.27 (Stub1 protein, mouse)
RN  - EC 1.1.1.27 (L-Lactate Dehydrogenase)
SB  - IM
MH  - Animals
MH  - Male
MH  - Mice
MH  - *Lactic Acid/metabolism
MH  - *Sertoli Cells
MH  - Transcriptional Activation/genetics
MH  - Ubiquitination
MH  - L-Lactate Dehydrogenase
OTO - NOTNLM
OT  - Lactate
OT  - Lactate dehydrogenase A (LDHA)
OT  - STIP1 homology and U-box-containing protein 1 (STUB1)
OT  - Sertoli cells (SCs)
OT  - Ubiquitination
EDAT- 2022/12/28 06:00
MHDA- 2023/05/12 07:06
CRDT- 2022/12/27 23:29
PHST- 2022/04/11 00:00 [received]
PHST- 2022/11/06 00:00 [accepted]
PHST- 2023/05/12 07:06 [medline]
PHST- 2022/12/28 06:00 [pubmed]
PHST- 2022/12/27 23:29 [entrez]
AID - 10.1007/s00441-022-03705-x [pii]
AID - 10.1007/s00441-022-03705-x [doi]
PST - ppublish
SO  - Cell Tissue Res. 2023 May;392(2):565-579. doi: 10.1007/s00441-022-03705-x. Epub 
      2022 Dec 28.