FRINK Linked Data Fragments server

Matches in SemOpenAlex for { <https://semopenalex.org/work/W1994490290> ?p ?o ?g. }

• W1994490290 endingPage "3163" @default.
• W1994490290 startingPage "3163" @default.
• W1994490290 abstract "Orderly progression through the cell cycle is controlled by regulatory complexes which include cyclin-dependent kinases (CDK) and their negative regulators, CDK inhibitors (CKI). p27Kip1 is one of the major CKI that controls normal cellular proliferation and whose dysregulation has been implicated in malignant transformation1. In addition to its cell cycle-related function, p27Kip1 has emerged as a critical regulator of cell motility and migration by influencing the cytoskeleton via direct interaction with actin and/or microtubule (MT)-regulatory proteins.2,3 Stathmin (STMN1) is a MT destabilizing protein which has been previously identified as a p27Kip1 binding partner in modulating cell migration in vitro.3STMN1 is a highly conserved cytoplasmic protein which plays a pivotal role in MT dynamics both in interphase and mitosis.4 STMN1 acts as a MT destabilizer by promoting microtubule depolymerization and sequestering tubulin heterodimers thus preventing their polymerization. A tight regulation of STMN1 expression is critical for proper cell cycle progression. Overexpression of STMN1 characterizes a broad range of human malignancies and correlates strongly with advanced disease stages, metastasis and poor prognosis.5 While there is convincing evidence for a role of STMN1 up-regulation in maintaining the malignant phenotype, recent observations indicate that this role might not be exclusively related to its MT-regulatory function but to interactions with other molecules which are implicated in human cancer.This concept is supported by an elegant study by Berton and colleagues describing yet another facet of the functional relationship between p27Kip1 and STMN.6 Given the roles of both proteins in cellular proliferation and building on the original findings of STMN1-p27Kip1 interaction in vitro,3 the authors interrogated the functional relevance of such interaction in vivo. Utilizing a double knock-out (DKO) mouse model in which both p27Kip1 and STMN1 were deleted, they demonstrated that p27Kip1 and STMN1 cooperate in controlling cellular proliferation in vivo. Through carefully designed phenotypical analyses they showed that loss of STMN1 in the p27Kip1-null background rescued the increased body and organ size that characterizes p27Kip1KO in mice. Examination of cellular proliferation in DKO mice revealed that suppression of STMN1 prevented cellular proliferation in various tissues, including the retina basal layer, pituitary gland and thymus. More importantly, the development of pituitary adenomas, which occurs upon the sole depletion of p27Kip1, was prevented when p27Kip1 and STMN1 were depleted concomitantly. These findings support the idea that, at least in certain cell types, p27Kip1 and STMN1 may work together to regulate cellular proliferation.In order to understand the underlying mechanisms of these phenotypical changes, the authors asked if the major CDKs/cyclin complexes are responsible for mediating p27Kip1 and STMN1interaction in DKO animals. Surprisingly, they found that the absence of STMN1 in p27Kip1-null context influenced the activity of CDK4/6-cyclin D3 rather than the expected CDK2-cyclin A2 complexes. These findings were further correlated with the gene expression profiles which suggested that p27Kip1-STMN1 may affect cell cycle by disrupting intracellular signaling cascades triggered by external stimuli (e.g. JAK-STAT, MAPK). These preliminary results should prompt future research to determine if STMN1 phosphorylation status, which is known to drive its cellular activities, is influenced by p27Kip1 suppression. This would be particularly relevant as STMN1 is a phosphorylation substrate not only for components of the signaling pathways revealed by this study but also for p27Kip1-regulated CDKs.The findings reported by Berton et al. represent an important step in understanding the mechanisms by which p27Kip1 and STMN1 might cooperate in controlling normal and malignant cell proliferation. Yet, more research is needed to provide definitive proof for a direct physical interaction between p27Kip1 and STMN1 in vivo. The anti-proliferative function of STMN1 inhibition has been widely documented in various systems5 which makes it entirely possible that suppression of STMN1would rescue the hyper-proliferative phenotype of the p27Kip1KO mice through mechanisms independent of its potential relationship with p27Kip1. Nonetheless, this study opens new lines of investigation that will undoubtedly clarify the precise role of the p27Kip1-STMN1 regulatory loop in human disease. Intriguingly, increased STMN1 levels were recently shown to correlate with reduced cytoplasmic p27Kip1 expression in human extrahepatic cholangiocarcinoma (EHCC) and suppression of STMN1 in EHCC cells resulted in accumulation of p27Kip1 coupled with reduced proliferation.7 It is therefore crucial to further define and validate the aberrant p27Kip1-STMN1 axis in human cancer as it may hold promise for potential therapeutic targeting." @default.
• W1994490290 created "2016-06-24" @default.
• W1994490290 creator A5026108947 @default.
• W1994490290 creator A5086795238 @default.
• W1994490290 date "2014-10-15" @default.
• W1994490290 modified "2023-09-23" @default.
• W1994490290 title "p27^Kip1and STMN1: Partners again?" @default.
• W1994490290 cites W1871213404 @default.
• W1994490290 cites W1974574293 @default.
• W1994490290 cites W1995590506 @default.
• W1994490290 cites W1996905549 @default.
• W1994490290 cites W1997058261 @default.
• W1994490290 cites W2003023385 @default.
• W1994490290 cites W2091729097 @default.
• W1994490290 doi "https://doi.org/10.4161/15384101.2014.966580" @default.
• W1994490290 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/4613596" @default.
• W1994490290 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/25485493" @default.
• W1994490290 hasPublicationYear "2014" @default.
• W1994490290 type Work @default.
• W1994490290 sameAs 1994490290 @default.
• W1994490290 citedByCount "1" @default.
• W1994490290 countsByYear W19944902902019 @default.
• W1994490290 crossrefType "journal-article" @default.
• W1994490290 hasAuthorship W1994490290A5026108947 @default.
• W1994490290 hasAuthorship W1994490290A5086795238 @default.
• W1994490290 hasBestOaLocation W19944902901 @default.
• W1994490290 hasConcept C54355233 @default.
• W1994490290 hasConcept C86803240 @default.
• W1994490290 hasConcept C95444343 @default.
• W1994490290 hasConceptScore W1994490290C54355233 @default.
• W1994490290 hasConceptScore W1994490290C86803240 @default.
• W1994490290 hasConceptScore W1994490290C95444343 @default.
• W1994490290 hasIssue "20" @default.
• W1994490290 hasLocation W19944902901 @default.
• W1994490290 hasLocation W19944902902 @default.
• W1994490290 hasLocation W19944902903 @default.
• W1994490290 hasLocation W19944902904 @default.
• W1994490290 hasOpenAccess W1994490290 @default.
• W1994490290 hasPrimaryLocation W19944902901 @default.
• W1994490290 hasRelatedWork W1991523530 @default.
• W1994490290 hasRelatedWork W2002128513 @default.
• W1994490290 hasRelatedWork W2020824267 @default.
• W1994490290 hasRelatedWork W2020838698 @default.
• W1994490290 hasRelatedWork W2031436818 @default.
• W1994490290 hasRelatedWork W2057739827 @default.
• W1994490290 hasRelatedWork W2075354549 @default.
• W1994490290 hasRelatedWork W2112463916 @default.
• W1994490290 hasRelatedWork W2119103177 @default.
• W1994490290 hasRelatedWork W2092874662 @default.
• W1994490290 hasVolume "13" @default.
• W1994490290 isParatext "false" @default.
• W1994490290 isRetracted "false" @default.
• W1994490290 magId "1994490290" @default.
• W1994490290 workType "article" @default.