Induction of apoptosis increases SUMO-1 protein expression and conjugation in mouse periovulatory granulosa cells in vitro

Shao, Ruijin; Rung, Emilia; Weijdegård, Birgitta; Billig, Håkan

doi:10.1002/mrd.20386

Cited by 15 publications

(16 citation statements)

References 59 publications

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“…In previous studies, P 4 inhibited apoptosis in rat endometrial epithelial cells, which expressed functional nuclear PR in vitro (51), whereas RU-486 induced apoptosis in rabbit uterine epithelium in vivo (57). Our laboratory has also demonstrated that PR antagonists induce apoptosis in mouse ovarian granulosa cells that were expressing nuclear PR in vivo (62) and in vitro (63). These demonstrations suggest that the suppression of apoptosis is likely mediated by existence of nuclear PR in P 4 target tissues.…”

Section: Discussionmentioning

confidence: 67%

Nuclear progesterone receptor A and B isoforms in mouse fallopian tube and uterus: implications for expression, regulation, and cellular function

Shao

Weijdegård²,

Ljungström³

et al. 2006

American Journal of Physiology-Endocrinology and Metabolism

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Progesterone and its interaction with nuclear progesterone receptors (PR) PR-A and PR-B play a critical role in the regulation of female reproductive function in all mammals. However, our knowledge of the regulation and possible cellular function of PR protein isoforms in the fallopian tube and uterus in vivo is still very limited. In the present study, we revealed that equine chorionic gonadotropin (eCG) treatment resulted in a time-dependent increase in expression of both isoforms, reaching a maximal level at 48 h in the fallopian tube. Regulation of PR-A protein expression paralleled that of PR-B protein expression. However, in the uterus PR-B protein levels increased and peaked earlier than PR-A protein levels after eCG treatment. With prolonged exposure to eCG, PR-B protein levels decreased, whereas PR-A protein levels continued to increase. Furthermore, subsequent treatment with human (h)CG decreased the levels of PR protein isoforms in both tissues in parallel with increased endogenous serum progesterone levels. To further elucidate whether progesterone regulates PR protein isoforms, we demonstrated that a time-dependent treatment with progesterone (P4) decreased the expression of PR protein isoforms in both tissues, whereas decreases in p27, cyclin D2, and proliferating cell nuclear antigen protein levels were observed only in the uterus. To define the potential PR-mediated effects on apoptosis, we demonstrated that the PR antagonist treatment increased the levels of PR protein isoforms, induced mitochondrial-associated apoptosis, and decreased in epidermal growth factor (EGF) and EGF receptor protein expression in both tissues. Interestingly, immunohistochemistry indicated that the induction of apoptosis by PR antagonists was predominant in the epithelium, whereas increase in PR protein expression was observed in stromal cells of both tissues. Taken together, these observations suggest that 1) the tissue-specific and hormonal regulation of PR isoform expression in mouse fallopian tube and uterus, where they are potentially involved in regulation of mitochondrial-mediated apoptosis depending on the cellular compartment; and 2) a possible interaction between functional PR protein and growth factor signaling may have a coordinated role for regulating apoptotic process in both tissues in vivo.

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Section: Discussionmentioning

confidence: 67%

Nuclear progesterone receptor A and B isoforms in mouse fallopian tube and uterus: implications for expression, regulation, and cellular function

Shao

Weijdegård²,

Ljungström³

et al. 2006

American Journal of Physiology-Endocrinology and Metabolism

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“…Recently Shao et al [13], [14] reported that Sumo-1, based on immunohistochemical analyses, is expressed in both healthy and atretic mouse granulosa cells in vivo , suggesting that Sumo-1 may function both during follicular development and atresia. We performed western blotting on protein extracts and immunofluorescence on sections of 4-week mouse ovaries, using specific antibodies for Foxl2, Pias1, Ubc9 and Sumo-1.…”

Section: Resultsmentioning

confidence: 99%

“…SUMO-1 protein is widely expressed in various tissues, and in particular it has already been reported in the entire granulosa cell population of all follicles, from primordial to early antral stage, in ovaries of immature mice [14]. Stimulation of LH receptors in granulosa cells results in down-regulation of SUMO-1 expression with concomitant induction of ovulation [14]. SUMO-1 has also been localized in male germ cells and somatic cells of mouse and rat testes [19] as well as in human male germ and somatic cells [20].…”

Section: Discussionmentioning

confidence: 98%

The Forkhead Transcription Factor Foxl2 Is Sumoylated in Both Human and Mouse: Sumoylation Affects Its Stability, Localization, and Activity

et al. 2010

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The FOXL2 forkhead transcription factor is expressed in ovarian granulosa cells, and mutated FOXL2 causes the blepharophimosis, ptosis and epicanthus inversus syndrome (BPES) and predisposes to premature ovarian failure. Inactivation of Foxl2 in mice demonstrated its indispensability for female gonadal sex determination and ovary development and revealed its antagonism of Sox9, the effector of male testis development. To help to define the regulatory activities of FOXL2, we looked for interacting proteins. Based on yeast two-hybrid screening, we found that FOXL2 interacts with PIAS1 and UBC9, both parts of the sumoylation machinery. We showed that human FOXL2 is sumoylated in transfected cell lines, and that endogenous mouse Foxl2 is comparably sumoylated. This modification changes its cellular localization, stability and transcriptional activity. It is intriguing that similar sumoylation and regulatory consequences have also been reported for SOX9, the male counterpart of FOXL2 in somatic gonadal tissues.

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“…A variety of stress conditions, including elevated temperature, ethanol or H 2 O 2 exposure, and hypertonic conditions have been shown to cause changes in the sumoylation pattern for both vertebrates [41,46], yeast [32], and plant [45] cells. In addition to changes in response to stressors, significant changes in overall sumoylation patterns have also been observed for normal differentiating cells [42,47], during induction of apoptosis [48], and for cancerous cells [28]. These combined results suggest the sumoylation contributes to multiple cellular processes that are activated by changes in cellular environment.…”

Section: Conditional Sumoylationmentioning

confidence: 88%

Ubiquitin proteolytic system: focus on SUMO

Wilson¹,

Heaton²

2008

Expert Review of Proteomics

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The Small Ubiquitin-like Modifier proteins (Smt3 in yeast and SUMOs 1-4 in vertebrates) are members of the ubiquitin super family. Like ubiquitin, the SUMOs are protein modifiers that are covalently attached to the epsilon amino group of lysine residues in the substrates. The application of proteomics to the SUMO field has greatly expanded both the number of known targets and the number of identified target lysines. As new refinements of proteomic techniques are developed and applied to sumoylation, an explosion of novel data is likely in the next five years. This ability to examine sumoylated proteins globally, rather than individually, will lead to new insights into both the functions of the individual SUMO types and to how dynamic changes in overall sumoylation occur in response to alterations in cellular environment. In addition, there is a growing appreciation for the existence of crosstalk mechanisms between the sumoylation and ubiquitinylation processes. Rather than being strictly parallel, these two systems have many points of intersection, and It is likely that coordination of these two systems is a critical contributor to the regulation of many fundamental cellular events. KeywordsMass spectrometry; Proteomics; Tandem Affinity Purification; Cross-talk; Signature Tags; STUbL; Ubl; SUMOeome SUMOs and the ubiquitin super familyThe small protein modifier, ubiquitin, is the prototype of the ubiquitin superfamily [1]. The biochemistry of ubiquitinylation is well understood as is the role of polyubiquitinylation in targeting proteins for proteasomal degradation. Over the last decade, a number of ubiquitinlike proteins (Ulps) have been discovered, including the SUMO family (Smt3 in yeast and SUMOs 1-4 in vertebrates), whose biological functions are less well-defined. The three most well-characterized vertebrate SUMOs fall into two subfamilies, SUMO1 and SUMO2/3. SUMO2 and SUMO3 share 95% sequence identity compared to only ~ 50% identity between SUMO2/3 and SUMO1, though the common and distinct functional roles of the various SUMOs has not been clearly delineated. While SUMO1 shares only about 18% with ubiquitin, all the Ulps have very similar tertiary structures with a common ubiquitin fold and a C-terminal diglycine in the mature forms. Like ubiquitin, SUMOs are post-translationally attached to target protein lysine residues using an enzymatic pathway that is biochemically analogous to, but functionally distinct from the classical ubiquitinylation system [2]. The overall process has four steps ( Fig. 1): 1) processing of the precursor SUMO by SUMO proteases (SENPS) which remove C-terminal residues to expose the diglycine motif, 2)

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Induction of apoptosis increases SUMO-1 protein expression and conjugation in mouse periovulatory granulosa cells in vitro

Cited by 15 publications

References 59 publications

Nuclear progesterone receptor A and B isoforms in mouse fallopian tube and uterus: implications for expression, regulation, and cellular function

Nuclear progesterone receptor A and B isoforms in mouse fallopian tube and uterus: implications for expression, regulation, and cellular function

The Forkhead Transcription Factor Foxl2 Is Sumoylated in Both Human and Mouse: Sumoylation Affects Its Stability, Localization, and Activity

Ubiquitin proteolytic system: focus on SUMO

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