Activating transcription factor or cAMP-dependent transcription factor ATF-2, also known as CRE-BP1, regulates the transcription of various genes, including those involved in anti-apoptosis, cell growth, and DNA damage response. ATF-2 needs to be phosphorylated by Jun N-terminal kinase (JNK), p38 (MAPK14), or extracellular-signal-regulated kinase 1 (ERK1) in order to be transcriptionally active. Activated ATF-2 then form dimers with proteins, such as members of the AP-1 family, and regulates gene transcription []. It has been implicated in several pathological conditions, including neurological diseases and cancer [, ].
This entry includes alcohol O-acetyltransferase 2 (Atf2) and N-acetyltransferase Sli1 from budding yeasts. Atf2 catalyses the esterification of isoamyl alcohol by acetyl coenzyme A []. Sli1 confers resistance to the sphingolipid biosynthesis inhibitor drug myriocin (ISP-1). It inactivates ISP-1 by converting it into N-acetyl-myriocin []. This entry also includes some uncharacterised proteins, such as YPL272C and C18B11.03c.
p38 kinases are mitogen-activated protein kinases (MAPKs), serving as important mediators of cellular responses to extracellular signals. They function in the regulation of the cell cycle, cell development, cell differentiation, senescence, tumorigenesis, apoptosis, pain development and pain progression, and immune responses. p38 kinases are activated by the MAPK kinases MKK3 and MKK6, which in turn are activated by upstream MAPK kinase kinases including TAK1, ASK1, and MLK3, in response to cellular stresses or inflammatory cytokines []. p38 substrates include other protein kinases and factors that regulate transcription, nuclear export, mRNA stability and translation. p38 kinases are drug targets for the inflammatory diseases psoriasis, rheumatoid arthritis, and chronic pulmonary disease [, ].Vertebrates contain four p38 kinases, named alpha, beta, gamma, and delta, which show varying substrate specificity and expression patterns.p38alpha/MAPK14 is expressed in most tissues and is the major isoform involved in the immune and inflammatory response. It is the central p38 MAPK involved in myogenesis []. It plays a role in regulating cell cycle check-point transition and promoting cell differentiation. p38alpha also regulates cell proliferation and death through crosstalk with the JNK pathway []. Its substrates include MAPK activated protein kinase 2 (MK2), MK5, and the transcription factors ATF2 and Mitf [].
