Preferred Label : Spermatogenesis Regulation Pathway;
NCIt related terms : Regulation of Spermatogenesis by CREM;
Alternative definition : BIOCARTA: The transcriptional regulator CREM plays a key role in spermatogenesis,
acting as a central transcription factor triggering a cascade of transcriptional activation
of post-meiotic genes involved in this process such as calspermin and testis angiotensin-converting
enzyme. The key role of CREM in sperm formation is demonstrated by the male sterility
of mice lacking CREM, the failure of spermatids to develop into mature sperm, and
a lack of post-meiotic gene expression in these animals. Prior to meiosis, splice
variants of CREM act as antagonists of cAMP-dependent transcriptional activation,
but coordinate with spermatogenesis, the potent transcriptional activator CREM tau
splice variant is highly expressed. In other tissues CREM activates genes in response
to cAMP through phosphorylation and CBP association, but transcriptional activation
by CREM in male germ cells is CBP independent. Stimulation of spermatids with follicle-stimulating
hormone (FSH) induces cAMP formation, and the association of CREM with the coactivator
ACT, although the mechanism regulating the interaction of CREM with ACT is not yet
known. A two-hybrid screen looking for ACT interacting factors revealed another surprising
component regulating CREM, the kinesin Kif17b. Kinesins are molecular motors that
interact with microtubules to transport organelles and other material within the cell.
Kif17b is actively exported from the nucleus in a Crm1-dependent manner, so when it
is bound to ACT the export of Kif17b excludes CREM-ACT from the nucleus and blocks
transcriptional activation by this complex. The mechanism regulating the interaction
of Kif17b with ACT to drive CREM activation is not yet known. Although the regulation
of transcription by a kinesin is surprising, a functional connection between cytoskeletal
elements and transcriptional regulation is not unprecedented, as demonstrated by the
transcription factor MIZ-1 that regulates transcription in response to changes in
microtubule structure. (This definition may be outdated - see the DesignNote.);
NCIt note : The BIOCARTA Definition (ALT_DEFINITION) for this pathway concept was provided by
BioCarta. This property was not created by, nor is it maintained by the NCI Thesaurus
staff. Additionally, BioCarta is no longer updating its pathway data; thus, the BIOCARTA
Definition might be outdated or inaccurate. Please see the Terms and Conditions for
Use at http://www.biocarta.com/.;
Biocarta ID : h_cremPathway;
Origin ID : C39037;
UMLS CUI : C1519448;
Semantic type(s)
- has_gene_product_element
- pathway_has_gene_element
